Risk-shifting Through Issuer Liability and Corporate Monitoring

This article explores how issuer liability re-allocates fraud risk and how risk allocation may reduce the incidence of fraud. In the US, the apparent absence of individual liability of officeholders and insufficient monitoring by insurers under-mine the potential deterrent effect of securities litigation. The underlying reasons why both mechanisms remain ineffective are collective action problems under the prevailing dispersed ownership structure, which eliminates the incentives to moni-tor set by issuer liability. This article suggests that issuer liability could potentially have a stronger deterrent effect when it shifts risk to individuals or entities holding a larger financial stake. Thus, it would enlist large shareholders in monitoring in much of Europe. The same risk-shifting effect also has implications for the debate about the relationship between securities litigation and creditor interests. Credi-tors’ claims should not be given precedence over claims of defrauded investors (e.g., because of the capital maintenance principle), since bearing some of the fraud risk will more strongly incentivise large creditors, such as banks, to monitor the firm in jurisdictions where corporate debt is relatively concentrated

Characteristics and Predictors of Patient Care Performed by Clinical Department Chairpersons at U.S. Schools of Pharmacy

Background Clinical pharmacy or pharmacy practice departments at schools of pharmacy are usually composed of practicing pharmacy specialists. There is little known about the requirements for and frequency of patient care provided by clinical department chairpersons. The primary objective of this study was to determine the likelihood that pharmacy practice chairs engage in patient care. A secondary objective was to identify those factors predicting chairperson participation in patient care activities. Methods A brief 22-item adaptive response survey was sent to clinical department chairpersons at schools of pharmacy in the United States. Initial identification of chairs came from the American Association of Colleges of Pharmacy (AACP) with verification by school websites. Surveys from schools without a clinical chairperson (or similar position) were excluded, as were surveys from schools with Ph.D. department chairpersons from blended departments (ie, Clinical with Outcomes/Policy Sciences). Results Of the 128 eligible schools\u27 department chairpersons, 113 completed the surveys (88.3% response rate). Forty-four (38.9%) chairs reported that they maintain an active clinical practice even though 103 (91.1%) report it is not required. Factors that had a significant association with clinical practice were clinical service being an expectation (P = .0004), having a practice prior to becoming chairperson (P = .001), having a higher clinical service expectation (P \u3c .0001), and having a lower administrative percentage (P = .0003). Age, rank, and academic track were not significant predictors. Of those with clinical practice, sites included community (45.4%), acute care (38.6%), primary care (4.5%), and other settings (11.4%). A majority of those with practice reported providing direct patient care (81.8%) or indirectly via supervision of students or other trainees (61.4%). Conclusions Most schools of pharmacy do not require clinical department chairpersons to maintain a patient care practice, but many still choose to practice. Those that practiced before becoming a chairperson and have a lower administrative burden are more likely to continue to provide patient care

Emergence of infective endocarditis due to Serratia spp.: Results of a multicenter cohort

BACKGROUND: Infective endocarditis due to METHODS: This was a retrospective analysis of adults treated for S-IE at 4 academic health systems in different US states from 2015 to 2021. Multivariable logistic regression analyzed the association of inpatient mortality with procedural management and combination antibiotic treatment. RESULTS: A total of 159 cases of S-IE were identified with a qualitative overall increase across the period, and a peak in 2019, although trends varied by site. Seventy-five were due to IDU, 57% involved a single left-sided valve, and inpatient mortality was 21%. In adjusted analyses, including 117 cases from 3 sites, lower inpatient mortality was associated with procedural intervention (odds ratio 0.14; 95% confidence interval, .03-.64) and combination antibiotic therapy (odds ratio 0.15; 95% confidence interval, .03-.74). DISCUSSION: In this multicenter study, we found that S-IE may be increasing, is commonly associated with IDU, is treated with varying strategies and carries high inpatient mortality. Procedural intervention and combination antibiotics were associated with lower mortality. Our study is limited by varying methods of case identification and a lack of data on clinical severity and surgical indications. Further study is urgently needed to define best management practices

Evaluating the Medication Regimen Complexity Score as a Predictor of Clinical Outcomes in the Critically Ill

Background: Medication Regimen Complexity (MRC) refers to the combination of medication classes, dosages, and frequencies. The objective of this study was to examine the relationship between the scores of different MRC tools and the clinical outcomes. Methods: We conducted a retrospective cohort study at Roger William Medical Center, Providence, Rhode Island, which included 317 adult patients admitted to the intensive care unit (ICU) between 1 February 2020 and 30 August 2020. MRC was assessed using the MRC Index (MRCI) and MRC for the Intensive Care Unit (MRC-ICU). A multivariable logistic regression model was used to identify associations among MRC scores, clinical outcomes, and a logistic classifier to predict clinical outcomes. Results: Higher MRC scores were associated with increased mortality, a longer ICU length of stay (LOS), and the need for mechanical ventilation (MV). MRC-ICU scores at 24 h were significantly (p \u3c 0.001) associated with increased ICU mortality, LOS, and MV, with ORs of 1.12 (95% CI: 1.06–1.19), 1.17 (1.1–1.24), and 1.21 (1.14–1.29), respectively. Mortality prediction was similar using both scoring tools (AUC: 0.88 [0.75–0.97] vs. 0.88 [0.76–0.97]. The model with 15 medication classes outperformed others in predicting the ICU LOS and the need for MV with AUCs of 0.82 (0.71–0.93) and 0.87 (0.77–0.96), respectively. Conclusion: Our results demonstrated that both MRC scores were associated with poorer clinical outcomes. The incorporation of MRC scores in real-time therapeutic decision making can aid clinicians to prescribe safer alternatives

Implementation of screening, brief intervention, and referral to treatment (SBIRT) in the emergency department without additional resources

Patients who misuse substances present in inordinate numbers for emergency department (ED) services. Therefore, EDs are an important environment for identifying, intervening and connecting patients with treatment and recovery support to improve patient health and reduce healthcare utilization. EDs have largely depended on external funding or additional personnel to execute SBIRT. Our aim was to integrate SBIRT into the ED workflow and coordinate transfer to treatment and community support programs without added monetary/staff resources. Beginning in 2010, we worked cooperatively with a local ED to integrate SBIRT into the normal ED workflow. This program of screening, brief interventions and warm-handoff referral is dubbed “Safe Landing.” Efforts have focused on: training staff; embedding SBIRT tools into existing data systems; nurturing relationships with community treatment and recovery providers; developing protocols for a “warm-handoff” that would ensure patients who, in the context of a health crisis, express an immediate interest in following a road to recovery; and securing reimbursement for services. Over one-and-a-half years since implementation, 45,770 patients have been screened, with 7,996 assessed, 2,058 receiving a brief intervention, and 137 referred to treatment or recovery support. Multiple staff trainings have resulted in a palpable culture shift to patient advocacy and increasing compliance with SBIRT protocols. Screening and BI tracking tools embedded in the ED data systems continue to be enhanced. ED reimbursement for SBIRT began 10/2012, and cooperative relationships with treatment and recovery providers have diversified. We will discuss the implementation strategies employed to overcome challenges in operationalizing SBIRT in the ED. Challenges to be discussed include changes in key personnel, embedding SBIRT into the labyrinth of data systems, initial staff scepticism and evolving area treatment and recovery services organizations. Regardless, Safe Landing perseveres, and commitment by the local ED is stronger than ever

Impact of a Multimodal Antimicrobial Stewardship Program on Pseudomonas aeruginosa Susceptibility and Antimicrobial Use in the Intensive Care Unit Setting

Objective. To study the impact of our multimodal antibiotic stewardship program on Pseudomonas aeruginosa susceptibility and antibiotic use in the intensive care unit (ICU) setting. Methods. Our stewardship program employed the key tenants of published antimicrobial stewardship guidelines. These included prospective audits with intervention and feedback, formulary restriction with preauthorization, educational conferences, guidelines for use, antimicrobial cycling, and de-escalation of therapy. ICU antibiotic use was measured and expressed as defined daily doses (DDD) per 1,000 patient-days. Results. Certain temporal relationships between antibiotic use and ICU resistance patterns appeared to be affected by our antibiotic stewardship program. In particular, the ICU use of intravenous ciprofloxacin and ceftazidime declined from 148 and 62.5 DDD/1,000 patient-days to 40.0 and 24.5, respectively, during 2004 to 2007. An increase in the use of these agents and resistance to these agents was witnessed during 2008–2010. Despite variability in antibiotic usage from the stewardship efforts, we were overall unable to show statistical relationships with P. aeruginosa resistance rate. Conclusion. Antibiotic resistance in the ICU setting is complex. Multimodal stewardship efforts attempt to prevent resistance, but such programs clearly have their limits

Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140217/1/sur.2013.9999.pd

Child Opportunity Index and Pediatric Intensive Care Outcomes: A Multicenter Retrospective Study in the United States.

OBJECTIVES: To evaluate for associations between a childs neighborhood, as categorized by Child Opportunity Index (COI 2.0), and 1) PICU mortality, 2) severity of illness at PICU admission, and 3) PICU length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Fifteen PICUs in the United States. PATIENTS: Children younger than 18 years admitted from 2019 to 2020, excluding those after cardiac procedures. Nationally-normed COI category (very low, low, moderate, high, very high) was determined for each admission by census tract, and clinical features were obtained from the Virtual Pediatric Systems LLC (Los Angeles, CA) data from each site. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 33,901 index PICU admissions during the time period, median patient age was 4.9 years and PICU mortality was 2.1%. There was a higher percentage of admissions from the very low COI category (27.3%) than other COI categories (17.2-19.5%, p < 0.0001). Patient admissions from the high and very high COI categories had a lower median Pediatric Index of Mortality 3 risk of mortality (0.70) than those from the very low, low, and moderate COI groups (0.71) ( p < 0.001). PICU mortality was lowest in the very high (1.7%) and high (1.9%) COI groups and highest in the moderate group (2.5%), followed by very low (2.3%) and low (2.2%) ( p = 0.001 across categories). Median PICU LOS was between 1.37 and 1.50 days in all COI categories. Multivariable regression revealed adjusted odds of PICU mortality of 1.30 (95% CI, 0.94-1.79; p = 0.11) for children from a very low versus very high COI neighborhood, with an odds ratio [OR] of 0.996 (95% CI, 0.993-1.00; p = 0.05) for mortality for COI as an ordinal value from 0 to 100. Children without insurance coverage had an OR for mortality of 3.58 (95% CI, 2.46-5.20; p < 0.0001) as compared with those with commercial insurance. CONCLUSIONS: Children admitted to a cohort of U.S. PICUs were often from very low COI neighborhoods. Children from very high COI neighborhoods had the lowest risk of mortality and observed mortality; however, odds of mortality were not statistically different by COI category in a multivariable model. Children without insurance coverage had significantly higher odds of PICU mortality regardless of neighborhood

A Baker\u27s Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation

Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses

Nucleic acids are used in many therapeutic modalities, including gene therapy, but their ability to trigger host immune responses in vivo can lead to decreased safety and efficacy. In the case of adeno-associated viral (AAV) vectors, studies have shown that the genome of the vector activates Toll-like receptor 9 (TLR9), a pattern recognition receptor that senses foreign DNA. Here, we engineered AAV vectors to be intrinsically less immunogenic by incorporating short DNA oligonucleotides that antagonize TLR9 activation directly into the vector genome. The engineered vectors elicited markedly reduced innate immune and T cell responses and enhanced gene expression in clinically relevant mouse and pig models across different tissues, including liver, muscle, and retina. Subretinal administration of higher-dose AAV in pigs resulted in photoreceptor pathology with microglia and T cell infiltration. These adverse findings were avoided in the contralateral eyes of the same animals that were injected with the engineered vectors. However, intravitreal injection of higher-dose AAV in macaques, a more immunogenic route of administration, showed that the engineered vector delayed but did not prevent clinical uveitis, suggesting that other immune factors in addition to TLR9 may contribute to intraocular inflammation in this model. Our results demonstrate that linking specific immunomodulatory noncoding sequences to much longer therapeutic nucleic acids can “cloak” the vector from inducing unwanted immune responses in multiple, but not all, models. This “coupled immunomodulation” strategy may widen the therapeutic window for AAV therapies as well as other DNA-based gene transfer methods