Preventing moral conflicts in patient care: Insights from a mixed-methods study with clinical experts

Background and aim Healthcare professionals are regularly exposed to moral challenges in patient care potentially compromising quality of care and safety of patients. Preventive clinical ethics support aims to identify and address moral problems in patient care at an early stage of their development. This study investigates the occurrence, risk factors, early indicators, decision parameters, consequences and preventive measures of moral problems. Method Semi-structured expert interviews were conducted with 20 interprofessional healthcare professionals from 2 university hospitals in Basel, Switzerland. A Likert scale questionnaire was completed by the interviewees and analysed using descriptive and inferential statistics. Results Healthcare professionals are frequently exposed to a variety of moral problems, such as end-of-life decisions, resource allocation and assessing the patient's will or decisional capacity. Thirty-four different risk factors for moral problems are identified, e.g. patient vulnerability, divergent values or world views, inadequate resources or poor ethical climate. Twenty-one early indicators are recognised such as disagreement between healthcare professionals, patients and relatives, emotional disturbances, gut feeling or conflict of conscience. A variety of preventive measures are suggested and presented in a preventive clinical ethics support process model. The most helpful measures are early ethical conversations with colleagues, early team-internal ethical case discussions and an ethics-trained contact person on the ward. Ethics training, kerbside consultations, proactive ethics consultations, ethics screening and rounds are also considered helpful. Conclusions Clinical ethics support services should not only offer reactive and complex, but also proactive and low-threshold support for healthcare professionals, patients and relatives.

Identifying early indicators of secondary peritonitis in critically ill patients with cirrhosis

Ascitic fluid infection (AFI) is a life-threatening complication of cirrhosis. We aimed to identify early indicators of secondary peritonitis (SP), which requires emergency surgery, and to describe the outcomes of SP and spontaneous bacterial/fungal peritonitis (SBFP). Adults with cirrhosis and AFI admitted to 16 university or university-affiliated ICUs in France between 2002 and 2017 were studied retrospectively. Cases were identified by searching the hospital databases for relevant ICD-10 codes and hospital charts for AFI. Logistic multivariate regression was performed to identify factors associated with SP. Secondary outcomes were short- and long-term mortality and survivors’ functional outcomes. Of 178 included patients (137 men and 41 women; mean age, 58 ± 11 years), 21 (11.8%) had SP, confirmed by surgery in 16 cases and by abdominal computed tomography in 5 cases. Time to diagnosis exceeded 24 h in 7/21 patients with SP. By multivariate analysis, factors independently associated with SP were ascitic leukocyte count > 10,000/mm3 (OR 3.70; 95%CI 1.38–9.85; P = 0.009) and absence of laboratory signs of decompensated cirrhosis (OR 4.53; 95%CI 1.30–15.68; P = 0.017). The 1-year mortality rates in patients with SBFP and SP were 81.0% and 77.5%, respectively (Log-rank test, P = 0.92). Patients with SP vs. SBFP had no differences in 1-year functional outcomes. This multicenter retrospective study identified two indicators of SP as opposed to SBFP in patients with cirrhosis. Using these indicators may help to provide early surgical treatment.

Liquidity of Non-financial Corporations: Evidence from Bulgaria

The financial and economic crisis years ago put the development of enterprises in Bulgaria and around the world in an uncontrollable environment that is difficult to predict, and led to significant problems with their financial condition. As a result of a rare CoVid-19 pandemic in 2020, the economic situation has become more complicated and portends déjà vu in terms of negative effects on the economy and businesses. The numerous closures of businesses and entire sectors will undoubtedly lead to serious financial consequences related to liquidity problems and excessive indebtedness of Bulgarian enterprises. The main problem that provokes this study is the lack of summarized information on the state of corporate liquidity and the solvency levels of non-financial corporations in Bulgaria. The main purpose of the article is to examine the liquidity status of non-financial corporations in Bulgaria. This analysis is needed to prevent liquidity crises and to bring out early indicators to warn and counter the risks posed by deteriorating solvency. It will be essential for the liquidity assessment to derive average industry values of the indicators to guide the companies from the sectors regarding the recommended liquidity levels to which they should strive.

Vitiligo-Specific Soluble Biomarkers as Early Indicators of Response to Immune Checkpoint Inhibitors in Metastatic Melanoma Patients

Background: Immunotherapy with checkpoint inhibitors strongly improved the outcome of metastatic melanoma patients. However, not all the patients respond to treatment and identification of prognostic biomarkers able to select patients who would respond to this therapy is of outmost importance. Considering that development of vitiligo-like depigmentation in melanoma patients represents both an adverse event of immunotherapy and a favorable prognostic factor for overall survival, we analyzed known soluble biomarkers of vitiligo to validate them as early indicators of response to checkpoint inhibitors in metastatic melanoma.Methods: Fifty-seven patients with metastatic melanoma receiving anti-PD-1 checkpoint inhibitor immunotherapy were enrolled. Patient sera and plasma were evaluated for vitiligo biomarkers at pre-treatment and after 1 and 3 months of therapy. Patients were divided and analyzed according to the best overall response to treatment. Characteristic vitiligo proteins were analyzed by ELISA, while expression of circulating microRNAs, distinctive of vitiligo, was determined using real-time RT-PCR.Results: Basal serum CD25 levels were higher in stable and responder melanoma patients and remained higher during the first 3 months of anti-PD-1 therapy compared to non-responder patients. The chemokine CXCL9 was absent in non-responder patients before therapy beginning. Moreover, an increase of CXCL9 levels was observed at 1 and 3 months of therapy for all patients, although higher CXCL9 amounts were present in stable and responder compared to non-responder patients. Finally, higher levels of miR-19b, miR-25 and miR-16 were observed after 1 month of therapy in plasma of stable and responder compared to non-responder patients.Conclusions: Serum levels of CD25 and CXCL9 before and during the first months of treatment could represent biomarkers of response to anti-PD-1 immunotherapy in metastatic melanoma patients. Plasmatic miR-19b, miR-25 and miR-16 could also represent possible early biomarkers of response to anti-PD-1 treatment, but they must be validated in a higher number of patients.

Pre-vaccination and early B cell signatures predict antibody response to SARS-CoV-2 mRNA vaccine

SARS-CoV-2 mRNA vaccines are highly effective, although weak antibody responses are seen in some individuals with correlates of immunity that remain poorly understood. Here we longitudinally dissected antibody, plasmablast, and memory B cell (MBC) responses to the two-dose Moderna mRNA vaccine in SARS-CoV-2-uninfected adults. Robust, coordinated IgA and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses, but earlier and more intensely after dose two. Distinct antigen-specific MBC populations also emerged post-vaccination with varying kinetics. We identified antigen non-specific pre-vaccination MBC and post-vaccination plasmablasts after dose one and their spike-specific counterparts early after dose two that correlated with subsequent antibody levels. These baseline and response signatures can thus provide early indicators of serological efficacy and explain response variability in the population.

Ultra-Early Indicators of Acute Hypertriglyceridemic Pancreatitis May Influence Treatment Decision-Making By Chinese Doctors

Background: This study investigates whether ultra-early indicators can predict severity of acute hypertriyceridemic pancreatitis (HTGP) and affect clinical decisions. Methods: For this observational retrospective study, we analyzed data of 110 HTGP patients enrolled between January 2017 and February 2020. HTGP patients were categorized into mild acute pancreatitis (MAP) and moderately severe acute pancreatitis-severe acute pancreatitis (MSAP-SAP) groups, based on their final clinical outcomes. Demographic and clinical data were collected and ultra-early indicators (serum calcium, triglyceride (TG), interleukin-6(IL-6), D-dimer, hemoglobin A1c(HbAc1), arterial lactate) levels were measured within 6 hours of admission. A multivariate logistic regression analysis model and receiver operating characteristic curve were used to determine ultra-early indicators values of high-risk patients. The chi-square test method was applied to estimate the hospitalization time and associated complications in MSAP-SAP group post-plasma exchange within or more than 24 hours. Results: Among the 110 HTGP patients, 56 were in the MAP group whereas, 54 were in the MSAP-SAP group. TG, IL-6, D-dimer, HbAc1, and arterial lactate levels measured within 6 hours after admission were significantly higher in the MSAP-SAP group, but serum calcium was significantly lower, versus the mild AP group. IL-6, D-dimer and serum calcium were identified as the risk factors for MSAP-SAP and were potential ultra-early indicators for predicting HTGP severity within 6 hours of admission. MSAP-SAP patients that underwent blood purification therapy within 24 hours of admission had a shorter hospitalization time than those treated 24 hours post-admission. Conclusion: The present study reveals IL-6, D-dimer, and serum calcium - ultra-early indicators - as promising biomarkers in the assessment of AP severity in HTGP patients within 6 hours. Early blood purification presents a novel therapy among MSAP-SAP patients within 24 hours and is associated with fewer complications and a shorter hospitalization time. However, traditional therapy can be further integrated to manage MAP patients effectively with less medical expenses.