The development and validation of a conceptual definition of avoidable transitions from long-term care to the emergency department: A mixed methods study.

Background/Objectives: Transitions to and from Emergency Departments (EDs) can be detrimental to long-term care (LTC) residents and burden the healthcare system. While reducing avoidable transfers is imperative, various terms are used interchangeably including inappropriate, preventable, or unnecessary transitions. Our study objectives were to develop a conceptual definition of avoidable LTC-ED transitions and to verify the level of stakeholder agreement with this definition. Methods: The EXamining Aged Care Transitions study adopted an exploratory sequential mixed-method design. The study was conducted in 2015-2016 in 16 LTC facilities, 1 ED, and 1 Emergency Medical Service (EMS) in a major urban center in western Canada. Phase 1 included 80 participants, (healthcare aides, licensed practical nurses, registered nurses, LTC managers, family members of residents, and EMS staff). We conducted semistructured interviews (n = 25) and focus groups (n = 19). In Phase 2, 327 ED staff, EMS staff, LTC staff, and medical directors responded to a survey based on the qualitative findings. Results: Avoidable transitions were attributed to limited resources in LTC, insufficient preventive care, and resident or family wishes. The definition generated was: A transition of an LTC resident to the ED is considered avoidable if: (a) Diagnostic testing, medical assessment, and treatment can be accessed in a timely manner by other means; (b) the reasons for a transfer are unclear and the transition would increase the disorientation, pain, or discomfort of a resident, outweighing a clear benefit of a transfer; and (c) the transition is against the wishes expressed by the resident over time, including through informal and undocumented conversations. There was a high level of agreement with the definition across the four participant groups. Conclusions and Implications: To effectively reduce LTC resident avoidable transitions, stakeholders must share a common definition. Our conceptual definition may significantly contribute to improved care for LTC residents.

A cysteine-specific solubilizing tag strategy enables efficient chemical protein synthesis of difficult targets.

We developed a new cysteine-specific solubilizing tag strategy via a cysteine-conjugated succinimide. This solubilizing tag remains stable under common native chemical ligation conditions and can be efficiently removed with palladium-based catalysts. Utilizing this approach, we synthesized two proteins containing notably difficult peptide segments: interleukin-2 (IL-2) and insulin. This IL-2 chemical synthesis represents the simplest and most efficient approach to date, which is enabled by the cysteine-specific solubilizing tag to synthesize and ligate long peptide segments. Additionally, we synthesized a T8P insulin variant, previously identified in an infant with neonatal diabetes. We show that T8P insulin exhibits reduced bioactivity (a 30-fold decrease compared to standard insulin), potentially contributing to the onset of diabetes in these patients. In summary, our work provides an efficient tool to synthesize challenging proteins and opens new avenues for exploring research directions in understanding their biological functions.

Larger stem to bone diameter ratio predicts lower cemented endoprosthesis failure.

BACKGROUND AND OBJECTIVES: With continued advances in treatment options, patients with endoprosthetic reconstruction are living longer and consequently relying upon their devices for a longer duration. Major causes of endoprosthesis failure include aseptic loosening and mechanical failure. In the setting of tumor resection, loss of bone stock and use of radiation therapy increase the risk for these complications. As such, considerations of remaining native bone and stem length and diameter may be increasingly important. We asked the following questions: (1) What was the overall rate of endoprosthesis failure at a minimum of 5-year follow-up? (2) Does resection length increase implant failure rates? (3) Does implant size and its ratio to cortical width of bone alter implant failure rates? METHODS: We retrospectively analyzed patient outcomes at a single institution between the years of 1999-2022 who underwent cemented endoprosthetic reconstruction at the hip or knee and identified 150 patients. Of these 150, 55 had a follow-up of greater than 5 years and were used for analysis. Radiographs of these patients at time of surgery were assessed and measured for resection length, bone diameter, stem diameter, and remaining bone length. Resection percentage, and stem to bone diameter ratios were then calculated and their relationship to endoprosthesis failure were analyzed. RESULTS: Patients in this cohort had a mean age of 55.8, and mean follow-up of 59.96 months. There were 78 distal femoral replacements (52%), 16 proximal femoral replacements (10.7%), and 56 proximal tibial replacements (37.3%). There were five patients who experienced aseptic loosening and six patients who experienced mechanical failure. Patients with implant failure had a smaller mean stem to bone diameter (36% vs. 44%; p = 0.002). A stem to bone diameter of 40% appeared to be a breaking point between success and failure in this series, with 90% of patients with implant failure having a stem: bone ratio less than 40%. Stem to bone ratio less than 40% increased risk for failure versus stems that were at least 40% the diameter of bone (6/19 [31.6%] vs. 0/36 [0%]; odds ratio 0.68; p < 0.001). Resection length did not appear to have an impact on the rates of aseptic loosening and mechanical failure in this series. CONCLUSIONS: Data from this series suggests a benefit to using stems with a larger diameter when implanting cemented endoprostheses at the hip or knee. Stems which were less than 40% the diameter of bone were substantially more likely to undergo implant failure.

Cost-effective, portable, patient-dedicated three-dimensional automated breast ultrasound for point-of-care breast cancer screening.

Breast cancer screening has substantially reduced mortality across screening populations. However, a clinical need persists for more accessible, cost-effective, and robust approaches for increased-risk and diverse patient populations, especially those with dense breasts where screening mammography is suboptimal. We developed and validated a cost-effective, portable, patient-dedicated three-dimensional (3D) automated breast ultrasound (ABUS) system for point-of-care breast cancer screening. The 3D ABUS system contains a wearable, rapid-prototype 3D-printed dam assembly, a compression assembly, and a computer-driven 3DUS scanner, adaptable to any commercially available US machine and transducer. Acquisition is operator-agnostic, involves a 40-second scan time, and provides multiplanar 3D visualization for whole-breast assessment. Geometric reconstruction accuracy was evaluated with a 3D grid phantom and tissue-mimicking breast phantoms, demonstrating linear measurement and volumetric reconstruction errors < 0.2 mm and < 3%, respectively. The system's capability was demonstrated in a healthy male volunteer and two healthy female volunteers, representing diverse patient geometries and breast sizes. The system enables comfortable ultrasonic coupling and tissue stabilization, with adjustable compression to improve image quality while alleviating discomfort. Moreover, the system effectively mitigates breathing and motion, since its assembly affixes directly onto the patient. While future studies are still required to evaluate the impact on current clinical practices and workflow, the 3D ABUS system shows potential for adoption as an alternative, cost-effective, dedicated point-of-care breast cancer screening approach for increased-risk populations and limited-resource settings.

Antagonistic Insulin Derivative Suppresses Insulin-Induced Hypoglycemia.

Insulin derivatives provide new functions that are distinctive from native insulin. We investigated insulin modifications on the C-terminal A chain with insulin receptor (IR) peptide binders and presented a full and potent IR antagonist. We prepared insulin precursors featuring a sortase A (SrtA) recognition sequence, LPETGG, at the C-terminal A chain and used a SrtA-mediated ligation method to synthesize insulin derivatives. The insulin precursor exhibits full IR agonism potency, similar to native human insulin. We explored derivatives with linear IR binding peptides attached to the insulin C-terminal A chain. One insulin derivative with an IR binder (Ins-AC-S2) can fully antagonize IR activation by insulin, as confirmed by cell-based assays. This IR antagonist suppresses insulin-induced hypoglycemia in a streptozotocin-induced diabetic rat model. This study provides a new direction toward insulin antagonist development.

Persistence of SARS-CoV-2 in saliva: Implications for late-stage diagnosis and infectious duration.

Saliva has been a COVID-19 diagnostic specimen of interest due to its simple collection, scalability, and yield. Yet COVID-19 testing and estimates of the infectious period remain largely based on nasopharyngeal and nasal swabs. We sought to evaluate whether saliva testing captured prolonged presence of SARS-CoV-2 and potential infectiousness later in the disease course. We conducted an observational study of symptomatic COVID-19 patients at University Hospital in Newark, NJ. Paired saliva and nasal specimens from 96 patients were analyzed, including longitudinal analysis of paired observations from 28 of these patients who had multiple time-points. Saliva detected significantly more cases of COVID-19 beyond 5 days (86.1% [99/115] saliva vs 48.7% [56/115] nasal, p-value < 0.001), 9 days (79.4% [50/63] saliva vs 36.5% [23/63] nasal, p-value < 0.001) and 14 days (71.4% [20/28] saliva vs 32.1% [9/28] nasal, p-value = 0.010) of symptoms. Additionally, saliva yielded lower cycle thresholds across all time periods, indicative of higher viral loads in saliva. In the longitudinal analysis, a log-rank analysis indicated that the survival curve for saliva was significantly different from the curve for nasal swabs (p<0.001) with a median survival time for saliva of 18 days compared to 13 days for nasal swabs. We additionally performed saliva viral cultures among a similar COVID-19 patient cohort and noted patients with positive saliva viral cultures between 7 to 28 days of symptoms. Findings from this study suggest that SARS-CoV-2 RNA persists longer and in higher abundance in saliva compared to nasal swabs, with potential of prolonged propagating virus. Testing saliva may thus increase yield for detecting potentially infectious virus even beyond the first five days of symptomatic COVID-19.

"More is not always better": Park's sweet spot theory-driven implementation strategy for viable optimal safe nurse staffing policy in practice.

AIM: This paper aims to propose Park's sweet spot theory-driven implementation strategy, which makes optimal safe staffing policy really work in nursing practice. BACKGROUND: For the last 40 years, mainstream nursing workforce research has emphasized that having more registered nurses leads to better patient outcomes, and yet staffing policies have failed to implement this crucial concept. Meanwhile, global nursing shortages have become rampant, a problem that only dilutes the skill-mix ratios in the nursing workforce. Low fertility and an aging population worldwide are then accelerating these shortages. These dire circumstances may be persisting because of unclear, unsubstantiated cost-efficiency in the nursing workforce. For this reason, there remains a dearth of well-researched evidence for a clear threshold on optimal safe staffing levels that could maximize quality of care relative to cost given limited healthcare financial budgets and which could also be fitted into each care setting. Along with that, an implementation strategy for optimal safe staffing levels is nonexistent. SOURCES OF EVIDENCE: An implementation strategy has been developed through interdisciplinary consilience-based theory synthesis of both prospective theory and regulatory focus theory combined with Park's optimized nursing staffing (sweet spot) estimation theory. DISCUSSION/CONCLUSIONS: A theory-driven novel implementation strategy is proposed, which functions as a nudge strategy that uses the synchronous balance of quality of care, nurse staffing, and cost. It illustrates (1) how to create shared value among patients, nurses, and stakeholders through robust evidence-based, informed shared decision-making rationales on the optimal safe nurse staffing levels and (2) how to induce stakeholders to overcome resistance to innovation and improve their nursing workforce through value chain in management science. IMPLICATIONS FOR NURSING WORKFORCE POLICY: This novel implementation strategy may be a viable solution to mitigate the nursing shortage by leading stakeholders (1) to compete with each other (on the basis of nursing sufficiency) and (2) to competitively demonstrate the patient-centered value (patient-perceived care quality relative to cost) of their institutions.

Toward mechatronic MRI-guided focal laser ablation of the prostate: Robust registration for improved needle delivery.

BACKGROUND: Multiparametric MRI (mpMRI) is an effective tool for detecting and staging prostate cancer (PCa), guiding interventional therapy, and monitoring PCa treatment outcomes. MRI-guided focal laser ablation (FLA) therapy is an alternative, minimally invasive treatment method to conventional therapies, which has been demonstrated to control low-grade, localized PCa while preserving patient quality of life. The therapeutic success of FLA depends on the accurate placement of needles for adequate delivery of ablative energy to the target lesion. We previously developed an MR-compatible mechatronic system for prostate FLA needle guidance and validated its performance in open-air and clinical 3T in-bore experiments using virtual targets. PURPOSE: To develop a robust MRI-to-mechatronic system registration method and evaluate its in-bore MR-guided needle delivery accuracy in tissue-mimicking prostate phantoms. METHODS: The improved registration multifiducial assembly houses thirty-six aqueous gadolinium-filled spheres distributed over a 7.3 × 7.3 × 5.2 cm volume. MRI-guided needle guidance accuracy was quantified in agar-based tissue-mimicking prostate phantoms on trajectories (N = 44) to virtual targets covering the mechatronic system's range of motion. 3T gradient-echo recalled (GRE) MRI images were acquired after needle insertions to each target, and the air-filled needle tracks were segmented. Needle guidance error was measured as the shortest Euclidean distance between the target point and the segmented needle trajectory, and angular error was measured as the angle between the targeted trajectory and the segmented needle trajectory. These measurements were made using both the previously designed four-sphere registration fiducial assembly on trajectories (N = 7) and compared with the improved multifiducial assembly using a Mann-Whitney U test. RESULTS: The median needle guidance error of the system using the improved registration fiducial assembly at a depth of 10 cm was 1.02 mm with an interquartile range (IQR) of 0.42-2.94 mm. The upper limit of the one-sided 95% prediction interval of needle guidance error was 4.13 mm. The median (IQR) angular error was 0.0097 rad (0.0057-0.015 rad) with a one-sided 95% prediction interval upper limit of 0.022 rad. The median (IQR) positioning error using the previous four-sphere registration fiducial assembly was 1.87 mm (1.77-2.14 mm). This was found to be significantly different (p = 0.0012) from the median (IQR) positioning error of 0.28 mm (0.14-0.95 mm) using the new registration fiducial assembly on the same trajectories. No significant difference was detected between the medians of the angular errors (p = 0.26). CONCLUSION: This is the first study presenting an improved registration method and validation in tissue-mimicking phantoms of our remotely actuated MR-compatible mechatronic system for delivery of prostate FLA needles. Accounting for the effects of needle deflection, the system was demonstrated to be capable of needle delivery with an error of 4.13 mm or less in 95% of cases under ideal conditions, which is a statistically significant improvement over the previous method. The system will next be validated in a clinical setting.

How, scholar, do you want to be remembered by future generations?: Finding your own balance between the ownership of knowledge and the freedom to pursue economic interests.

To assume that copyright just protects "expressions," (unlike "ideas" protected by patents), may be misleading because a particularly ordered procedure is also protected by copyright law. The procedure as well as the image of Park's Sweet Spot Theory require prior written permission from the original copyright holder for its use. Because this would stymie future generations from building further on this idea, I returned the theory-based patent to society so that prospective research and development will have no hindrances in the establishment of new knowledge/solutions in nursing science.

Novel neuroelectrophysiological age index associated with imaging features of brain aging and sleep disorders.

Sleep architecture and microstructures alter with aging and sleep disorder-led accelerated aging. We proposed a sleep EEG based brain age prediction model using convolutional neural networks. We then associated the estimated brain age index with brain structural aging features, sleep disorders and various sleep parameters. Our model also showed a higher BAI (predicted brain age minus chronological age) is associated with cortical thinning in various functional areas. We found a higher BAI for sleep disorder groups compared to healthy sleepers, as well as significant differences in the spectral pattern of EEG among different sleep disorders (lower power in slow and ϑ waves for sleep apnea vs. higher power in ß and σ for insomnia), suggesting sleep disorder-dependent pathomechanisms of aging. Our results demonstrate that the new EEG-BAI can be a biomarker reflecting brain health in normal and various sleep disorder subjects, and may be used to assess treatment efficacy.

Prevalence of elevated alanine aminotransferase (ALT) in pregnancy: A cross-sectional labor and delivery-based assessment.

Since liver tests are not routinely checked in pregnancy, the prevalence of abnormal liver tests and liver-related abnormalities in pregnancy in a US-based population is not known. We sought to determine the prevalence of abnormal alanine aminotransferase (ALT) among pregnant Individuals who present to labor and delivery for evaluation and to evaluate prevalence of underlying diagnosed liver conditions. Prospective study evaluating liver tests in consecutive samples obtained on the labor and delivery unit. Patient characteristics were compared between those with and without abnormal ALT and those with and without abnormal ALT without a liver-related diagnosis made in clinical practice, using t tests for continuous measures and χ2 or Fisher's exact tests as appropriate for categorical measures. Logistic regression was utilized to identify factors associated with abnormal ALT in this subcohort to determine predictors of abnormal ALT in those without a known liver-related diagnosis. We collected 1024 laboratory specimens from 996 patients. Of these patients, 131 of 996 (13.2%) had elevated ALT ≥25 IU/L; 20 (2%) had ALT ≥50, 6 (0.6%) had ALT ≥125 and 3 (0.3%) had ALT ≥250. 61/131 (46.6%) of patients with ALT ≥25 IU/L had not had LTs checked during routine pregnancy care. 20 (15%) of individuals with abnormal LT had preeclampsia; 5 (4%) had cholestasis of pregnancy; 1 (0.8%) had hepatitis C; there were no other chronic liver diseases diagnosed. There were no significant demographic or clinical differences between those with and without ALT ≥25, whether liver disease diagnosis was made or not. We identified an over 10% prevalence of abnormal LTs in consecutive pregnant individuals who presented to L&D, most of whom did not have a liver-related condition diagnosed in clinical practice. Among those with liver-related diagnoses, PE and ICP were the most common among individuals with ALT≥25 IU/mL, with chronic liver disease rarely diagnosed. Further evaluation of the role of ALT testing as part of routine prenatal care is needed, particularly in establishing a baseline prevalence of liver test abnormalities in pregnancy and independent association with pregnancy outcomes.

Potential effects of nicotine content in cigarettes on use of other substances.

A national nicotine reduction policy has the potential to reduce cigarette smoking and associated adverse health impacts among vulnerable populations. However, possible unanticipated adverse effects of reducing nicotine content in cigarettes, such as increasing the use of alcohol or other abused substances, must be examined. The purpose of this study was to evaluate the effects of exposure to varying doses of nicotine in cigarettes on use of other substances. This was a secondary analysis (n = 753) of three simultaneous, multisite, double-blind, randomized-controlled trials examining 12 weeks of exposure to study cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) among daily smokers from three vulnerable populations: individuals with affective disorders (n = 251), individuals with opioid use disorder (n = 256), and socioeconomically-disadvantaged women of reproductive age (n = 246). Effect of study cigarette assignment on urine toxicology screens (performed weekly) and responses to drug and alcohol use questionnaires (completed at study weeks 6 and 12) were examined using negative binomial regression, logistic regression, or repeated measures analysis of variance, controlling for sex, age, and menthol status. The most common substances identified using urine toxicology included tetrahydrocannabinol (THC; 44.8%), cocaine (9.2%), benzodiazepine (8.6%), and amphetamines (8.0%), with 57.2% of participants testing positive at least once for substance use (27.3% if excluding THC). No significant main effects of nicotine dose were found on any of the examined outcomes. These results suggest that reducing nicotine content does not systematically increase use of other substances, even among individuals at increased risk of substance use. ClinicalTrials.gov Identifiers: NCT02232737, NCT2250664, NCT2250534.

Strategic Significance of Low Viral Load of Human Papillomavirus in Uterine Cervical Cytology Specimens.

Infection with high-risk (HR) Human Papillomavirus (HPV) is associated with the development of precancerous lesions or invasive carcinoma of the uterine cervix. Thus, the high viral load (VL) of HR-HPV DNA currently serves as a representative quantitative marker for cervical cancer. However, the clinical significance of low HPV DNA VL remains undetermined. This study aimed to evaluate the clinical association between the low HPV DNA VL and cytology/histologic diagnosis of cervical samples. We searched the electronic medical databases for the resultant analyses of HPV genotyping among patients who underwent treatment for any cervical lesion or who had undergone gynecological examinations with any positive HPV results according to the national cancer screening service between 2015 and 2016. HPV testing with genotyping and semi-quantitative VL measurement was conducted using an AnyplexTM II H28 Detection assay (H28 assay, Seegene, Seoul, Republic of Korea). The H28 assay is a multiplex semi-quantitative real-time PCR test using the tagging of oligonucleotide cleavage and extension (TOCE) technology. The VL was semi-quantified as high (3+; positive signal before 31 PCR cycles), intermediate (2+; positive between 31 and 39 PCR cycles), or low (1+; positive after 40 PCR cycles). Out of 5940 HPV VL analyses, 356 assays (5.99%) were reported as low VL (1+) of HPV DNA. Matched cytology diagnoses were mostly negative findings (n = 347, 97.5%), except for seven cases of atypical squamous cells of undetermined significance (1.9%) and two cases of atypical glandular cells (0.6%). During the follow-up periods, abnormal cytologic diagnoses were identified, including one case of high-grade squamous intraepithelial lesion (HSIL) and two low-grade squamous intraepithelial lesions (LSILs). The matched, confirmative histologic diagnosis of HSIL cytology was compatible with chronic inflammation, wherein the two LSILs had regular check-ups. None revealed clinically concerned outcomes associated with HPV-related squamous lesions. The cytology was most likely negative for malignancy when the VL of HPV DNA was low (1+). Additional strategic monitoring and management may thus be unnecessary.

Nursing policy and practice in Mongolia: Issues and the way forward.

Global inequality exists in the availability of a nursing workforce, supported evidentially by the ratio, in low-income countries, of only 9.1 nurses per 10 000 people versus 107.7 nurses per 10 000 people in high-income countries. Mongolia is no exception with 42.14 nurses per 10 000 people and a nursing shortage severe enough to endanger patient safety and well-being. This paper details both a policy analysis and contextually well-designed recommendations to strengthen Mongolia's nursing science and practice systems. Obstacles that significantly affect the successful development of nursing and midwifery professions in Mongolia include (1) a lack of strategic planning and regulation; (2) low status of nurses and midwives; (3) absence of professional representation for nurses and midwives; and (4) a dearth of strategic programs for postgraduate training of nurses and midwives. The suggested recommendations include the appointment of a chief nursing office within the government and a cohort of nurse leaders to work to establish a nursing and midwifery board as an independent, professional regulatory body in Mongolia to develop and implement standards to ensure best practice, higher standards of nurse education, and regulate the profession.

Diffusion of Innovations-Informed Knowledge Translation Strategy to Implement Optimal Safe Nursing Workforce Policy in Practice.

AIM: This study aims to develop a free, limited-edition workshop as an effective knowledge translation strategy to enhance nurse leader-perceived self-efficacy for competence using Park's Sweet Spot Theory and to evaluate its effectiveness over time. METHOD: This is a study showing the process of developing a study protocol and its details. RESULTS: A 2-day workshop was developed for innovators and early adopters among nurse leaders with a macro-level influence based on Rogers's diffusion of innovations theory, which consists of an introduction of Park's Sweet Spot Theory, hands-on experience, a summary session, and a presentation of a certificate of completion. The workshop will be held at the University of Alberta Faculty of Nursing, using the "enabling blends" mode. A hybrid design of comparative effectiveness research and analysis of change will be utilized to assess nurse leader-perceived self-efficacy. CONCLUSION: This protocol is significant as the first step in providing scientific rationales on how to effectively implement new knowledge-optimal safe nurse staffing levels derived from Park's Sweet Spot Theory-into the right (safe yet efficient) nursing workforce policy-making to alleviate global nursing shortages.

No more unimplementable nurse workforce planning.

Objective: This paper aims to spur thought-provoking practical debates on current nurse workforce staffing and scheduling systems in relation to a critical review of Ang and colleagues' (2018) article entitled "Nurse workforce scheduling in the emergency department: A sequential decision support system considering multiple objectives."Design: Discussion paper on a practical discourse in connection with the aforementioned published article.Discussion: Mathematical Programming (optimisation) (MP)-based nursing research has been published for nearly thirty years almost exclusively in industrial engineering or health business administration journals, demonstrating a widening gap between nursing research and practice. Nurse scientists' knowledge and skill of MP is insufficient, as are their interdisciplinary collaborations, setting back the advancement of nursing science. Above all, nurse scientists skilled in decision science are desperately needed for that analytic intellection which is rooted in the 'intrinsic nature and value of nursing care.' It is imperative that nurse scientists be well-prepared for the new age of the Fourth Industrial Revolution through both an education in MP and interdisciplinary collaboration with decision science experts in order to prevent potential stereotyped MP-based algorithm-driven destructive influences.Conclusions: The current global nursing shortage makes optimal nursing workforce staffing and scheduling more important. MP helps nurse executives and leaders to ensure the most efficient number of nurses with the most effective composition of nurse staffing at the right time for a reasonable cost. Nurse scientists urgently need to produce a new nursing knowledge base that is directly implementable in nursing practice.Impact Statement: Nurse scientists should take the leading role in producing the mathematical programming-integrated knowledge base that is directly implementable in practice.