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Background: Housing instability in the United States is a critical social determinant of health, influencing health outcomes and health care utilization. This scoping review aimed to analyze literature on US health system screening and response programs addressing housing instability, highlighting methodologies, geographic and demographic variations, and policy implications., Methods: Adhering to PRISMA-ScR guidelines, the review included studies focusing on US health systems that screen and refer for housing instability. Major scholarly databases, including PubMed and Scopus, were queried. Screening and response program characteristics, methodologies, and outcomes were characterized., Results: Thirty studies published between 2003 and 2023 were included in this study. Included studies were primarily cross-sectional (26.7%) or quality improvement (20.0%), among 9 other designs. Screening programs were predominantly implemented in academic hospital systems (46.7%) and in the Northeast (63.3%). Of the 25 adult population studies, 68.0% were in outpatient settings, and of the 23 studies providing detailed information on their process, 52.2% used electronic health record entry. Of the 22 studies that describe their screening tool, 15 used institution-specific tools, and only 4 of the remaining 7 studies used identical tools. Of the 20 studies that described their response to positive screenings, 13 provided patients with a paper or electronic referral to a collaborating community partner, while only 6 aided the patient in connecting with community resources., Conclusion: This study found significant variability in screening and response programs for housing instability among US health care providers. A lack of standardized definitions and methodologies hampers effective comparison and implementation of these programs. Future research should focus on standardizing screening methods and measurement of interventions and outcomes to address housing instability., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Culture of safety (COS) is recognized as a critical component of patient safety but can be burdensome to measure due to survey length. This project aimed to develop a shortened COS survey with comparable measurement properties to a validated 19-item instrument., Methods: Item response theory (IRT) was used to reduce items from a 19-item COS survey at a 10-hospital health system. Using a 50% random sample, IRT was applied to evaluate survey question discrimination and information. Concepts from the key questions in each subdomain were reworded into a new abbreviated scale. Cognitive interviews with clinicians were conducted to validate reworded questions for adequacy, clarity, and consistency of interpretation., Results: The 19-item survey was reduced with IRT to 4 items. Cronbach's alpha for the 4-item IRT-derived scale was 0.80 (average inter-item covariance = 0.36) and was comparable to the original scale despite ∼75% reduction in items. Pearson correlation between the 4-item scale and the original scale was > 0.90. The 4-item scale demonstrated convergent validity. Results were replicated in a 50% random validation sample. Cognitive interviews revealed inadequacy of the shortened scale in assessing error-reporting culture. A fifth item was developed and qualitatively validated for this construct., Conclusion: Using a mixed methods approach, a lengthy COS survey was condensed and revised to a brief 5-question survey with comparable measurement properties and respondent interpretation. A shorter instrument necessarily loses detailed insight into multiple aspects of safety culture, and organizations should consider trade-offs in choosing to develop a briefer survey., (Copyright © 2022 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Background: The cost of surgical care is largely measured by charges or payments, both of which are inadequate. Actual cost data from the hospital's perspective are required to accurately quantify the financial return on investment of engaging in quality improvement. The objective of this study was to define the cost of individual, 30-day postoperative complications using robust cost data from a diverse group of hospitals., Methods: Using clinical data derived from the American College of Surgeons National Surgical Quality Improvement Program, this retrospective study assessed postoperative complications for patients who underwent surgery at one of four hospitals in 2016. Actual direct and indirect 30-day costs were obtained, and the adjusted cost per complication was determined., Results: From the 6,387 patients identified, the three complications associated with the highest independent adjusted cost per event were prolonged ventilation ($48,168; 95% confidence interval [CI]: $21,861-$74,476), unplanned intubation ($26,718; 95% CI: $15,374-$38,062), and renal failure ($18,528; CI: $17,076-$19,981). The three complications associated with the lowest independent adjusted cost per event were urinary tract infection (-$372; 95% CI: -$1,336-$592), superficial surgical site infection ($2,473; 95% CI: -$256-$5,201) and venous thromboembolism ($7,909; 95% CI: -$17,903-$33,721). After colectomy, the adjusted independent cost of anastomotic leak was $10,195 (95% CI: $5,941-$14,449), while the cost of postoperative ileus was $10,205 (95% CI: $6,259-$14,149)., Conclusion: The actual hospital costs of complications were estimated using cost data from four diverse hospitals. These data can be used by hospitals to estimate the financial benefit of reducing surgical complications., (Copyright © 2020 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Background: Evaluation of the effects of candidate drugs on the nervous system in preclinical safety pharmacology studies utilises a global neurobehavioral assessment, usually in the rat. This either takes the form of the functional observational battery (FOB) or modified Irwin Test, both of which evaluate effects across 4 functional domains: autonomic, neuromuscular, sensorimotor and behavioral. Although there is a great deal of overlap in the parameters they address, the two tests approach the assessments slightly differently. We undertook a broad pharmacological validation of both the FOB and the Irwin test, and compared the two outcomes., Methods: Male rats (6 per treatment group) were used to assess each of 12 reference drugs alongside vehicle controls in separate FOB and Irwin studies. The drugs compared in the two study types were chlorpromazine, chlordiazepoxide, clonidine, baclofen, (+)-amphetamine, harmaline, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, physostigmine, picrotoxin, yohimbine and atropine. There is a high degree of semantic equivalence in the parameters assessed in the autonomic domain between the two tests, with a lower degree of equivalence for neuromuscular and behavioral domains, whereas sensorimotor reflex testing in the FOB is far more extensive than in the Irwin test., Results: Across the set of reference drugs, concordance between the two tests was generally good across the 4 functional domains at the 'domain' level (i.e., detecting 'an effect'), whereas there was generally a poor concordance at the individual parameter level. However, this was partially explained by variability between repeated studies on a single reference drug using the same test (FOB or Irwin)., Conclusions: Both tests are 'fit-for-purpose' in detecting effects of candidate drugs on the nervous system. We would encourage the global safety pharmacology community to consider whether (a) the tests could be combined into one industry standard; (b) candidate drugs could be triaged according to CNS penetration, with the level of scrutiny in the CNS core battery assessment adjusted accordingly and (c) whether new home cage technology could be applied to semi-automate the preclinical neurobehavioral assessment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Patient Safety Indicator (PSI) 90 is a composite measure widely used in federal pay-for-performance and public reporting programs. A component metric of PSI 90, venous thromboembolism (VTE) rate, has been shown to be subject to surveillance bias and not a valid measure for hospital quality comparisons. A study was conducted to examine how hospital PSI 90 scores would change if the VTE measure were removed from calculation of this composite measure., Methods: Using 2014 Medicare inpatient claims data, PSI 90 scores were calculated with and without the VTE measure for 3,203 hospitals. Hospital characteristics obtained from the American Hospital Association Annual Survey and Centers for Medicare & Medicaid Services Payment Update Impact File were merged with PSI 90 scores., Results: Removing the VTE outcome measure from the calculation of PSI 90 version 5 improved PSI 90 scores for 17.1% of hospitals but lowered scores for 20.8% of hospitals, while 62.1% had no change in scores. Hospitals were more likely to improve on PSI 90 when the VTE measure was removed if they were larger (odds ratio [OR] = 1.60; 95% confidence interval [CI] = 1.00-2.58), were major teaching hospitals (OR = 1.76; 95% CI = 1.10-2.79), had greater technological resources (OR = 2.03; 95% CI = 1.40-2.94), or cared for sicker patients (OR = 1.12; 95% CI = 1.01-1.25)., Conclusion: Inclusion of the surveillance bias-prone VTE outcome measure in the PSI 90 composite disproportionately penalizes larger, academic hospitals and those that care for sicker patients. Removal of the VTE outcome measure from PSI 90 should be strongly considered., (Copyright © 2018 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Innate cells are essential for host defense against invading pathogens, and the induction and direction of adaptive immune responses to infection. We developed and optimized a flow cytometric assay that allows measurement of intracellular cytokine expression by monocytes, dendritic cells (DC) and granulocytes, as well as cellular uptake of green-fluorescent protein (GFP)-expressing mycobacteria, in very small volumes of peripheral blood. We show that innate cell stimulation resulted in increased granularity of monocytes and mDC and decreased granulocyte granularity that precluded flow cytometric discernment of granulocytes from monocytes and myeloid DC by forward and side scatter gating. Anti-CD66a/c/e antibody staining allowed reliable identification and exclusion of granulocytes for subsequent delineation of monocytes and myeloid DC. Intracellular cytokine expression by granulocytes, monocytes and mDC was remarkably sensitive to the dose of mycobacterial inoculum. Moreover, activation of monocytes and mDC with live BCG reduced expression levels of CD14 and CD11c, respectively, necessitating optimization of staining conditions to reliably measure these lineage markers. Finally, we characterized expression of IL-12/23p40, TNF-α, IL-6, and IL-10, by GFP(+) and GFP(-) monocytes and mDC from 25 healthy adults. This assay may be applied to the study of innate cell responses to any GFP-expressing pathogen, and can be performed on blood volumes as low as 200 μL per condition, making the assay particularly suitable for pediatric studies., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Antigen-specific proliferation is a critical function of memory T cells that is often utilised to measure vaccine immunogenicity and T cell function. We proposed that measurement of intracellular expression of the nuclear protein, Ki67, could reliably assess specific T cell proliferation in vitro. Ki67 was expressed in CD4+ and CD8+ T cells that had undergone in vitro proliferation after 6-day culture of human whole blood or PBMC with antigens. T cells cultured with no antigen did not express Ki67. When compared to current flow cytometry based proliferation assays, Ki67 detected proliferating cells with greater sensitivity than BrdU incorporation, whereas its sensitivity was similar to dye dilution of Oregon Green (OG), a CFSE derivative. Overall, the magnitude and cytokine expression profile of proliferating T cells detected by Ki67 expression correlated strongly with T cells detected with BrdU or OG. The intra-assay variability of Ki67 proliferation was 2-3% for CD4+ T cells, and 10-16% for CD8+ T cells. Finally, we demonstrate that the Ki67 assay detects tetanus toxoid-specific CD4+ T cell proliferation after infant vaccination with tetanus toxoid (TT). Overall our data suggest that intracellular Ki67 expression provides a specific, quantitative and reproducible measure of antigen-specific T cell proliferation in vitro., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: Although creating a culture of safety to support clinicians and improve the quality of patient care is a common goal among health care organizations, it can be difficult to envision specific efforts to directly influence organizational culture. To promote transparency and reinforce a nonpunitive attitude throughout the organization, a forum for the open, interdisciplinary discussion of patient safety problems--the Patient Safety Morbidity and Mortality (M&M) Conference--was created at Northwestern Memorial Hospital (Chicago). The intent of the M&M conference was to inform frontline providers about adverse events that occur at the hospital and to engage their input in root cause analysis, thereby encouraging reporting and promoting systems-based thinking among clinicians., Methods: Convened under the purview of the organization's quality program, and modeled on the traditional M&M conferences historically used by physicians, the conference is a monthly live meeting at which case studies are presented for retrospective (root cause) analysis by an interdisciplinary audience., Results: Since its start in 2003, approximately 60 patient safety M&M programs have been presented. Audiences typically represent a mix of physicians, nurses, pharmacists, management, therapists, and administrative and support staff. Staff perceptions of culture, as measured by the Hospital Survey on Patient Safety Culture, showed statistically significant improvements over time., Discussion: Ensuring the patient safety M&M conference program's sustained success requires an ongoing commitment to identifying events of clinical importance and to pursuing the productive discussion of these events in an open and safe forum. Patient safety M&M conferences are a valued opportunity to engage staff in exploring adverse events and to promote transparency and a nonpunitive culture.

Background: Unrelieved pain remains a critical problem in health care. Barriers to improving the state of pain control include lack of education of health care professionals. Traditional quality improvement (QI) strategies directed toward educational interventions are rarely sufficient to change pain-related practice. PAIN RESOURCE NURSE (PRN) PROGRAM: The PRN program consists of a two-day course, quarterly in-services, regular newsletters, a listserv, individual meetings with PRNs and their managers to plan and conduct quality initiatives appropriate to their unit, as well as an optional clinical experience., Results: Significant improvements were seen in knowledge and attitude of the participants, along with reduced turnover, improved patient satisfaction with pain control, a reduction in the prevalence of pain, and a greater percentage of patients who remembered speaking with a doctor or nurse about their pain (93% versus 89%)., Discussion: Establishing a PRN program entails conquering a number of management challenges common to any organizationwide QI project. The single most important step is building a shared priority among all those who must participate for success-in this case, nursing management., Summary: The PRN program is an effective strategy in creating organizational change to improve the state of pain control.

The chemokines are a family of signalling proteins that participate in regulation of the immune system and have been implicated in the pathogenesis of vascular diseases. Deleting the gene encoding the chemokine MCP-1 in mouse models of atherosclerosis reduces lipid lesion formation and circulating chemokines are upregulated in man immediately following myocardial infarction (MI) or coronary angioplasty. We have therefore investigated whether circulating levels of two chemokines (MCP-1 and eotaxin) differ between subjects with and without atherosclerosis. We have used three different methods of measuring the presence and extent of atherosclerosis in human subjects: duplex ultrasonography of the carotid arteries and clinical diagnosis of coronary heart disease on individuals from the general population and coronary angiography on patients with suspected heart disease. There was no difference in the levels of circulating MCP-1 or eotaxin, measured by ELISA, between subjects with and without atherosclerosis. Furthermore, any increase in circulating MCP-1 following acute MI must be short-lived, since chemokine levels were not different in subjects who had had an MI previously compared to those who had not. We conclude that although there may be a transient increase in circulating chemokine levels following coronary angioplasty, there is no difference in the levels of circulating MCP-1 or eotaxin in subjects with and without atherosclerosis.

Introduction: The Functional Observational Battery (FOB) is a systematic evaluation of nervous system function in the rat, comprising more than 30 parameters across autonomic, neuromuscular, sensorimotor and behavioural domains. We have collated FOB outcomes from 50 compounds that were not targeted at CNS disorders, and would therefore be anticipated to have relatively few CNS side-effects, for evaluation of the FOB as part of the safety pharmacology 'core battery'., Methods: Male Han Wistar rats (200-300 g) were used, with n=6 per treatment group. Each compound was tested acutely at 3 dose levels (oral route), from the therapeutic dose up to either 100 times this dose or to the maximal tolerated dose (MTD). A vehicle control group was included in each study., Results: Effects were detected in the FOB for 94% of compounds tested. The commonest effects were weight loss/decreased body weight gain overnight post-dose (46% of compounds), and changes in core temperature (36%). Dose-related effects were observed with 62% of compounds; the commonest was decreased body weight gain (32%), followed by effects on tail flick latency (14%), landing foot splay (12%), decreased rectal temperature (10%), time to exit the centre circle in the open field (10%), diarrhoea/loose faeces (8%), respiratory effects (4%), grasping reflex (4%) and supported rears in the open field (4%). Remaining parameters were affected by < or =2% of compounds., Discussion: The value of doing the FOB as part of the safety pharmacology 'core battery' is emphasised by the fact that, even for non-CNS targeted compounds, the majority affected at least one of the parameters in the FOB. These data may also help to anticipate the most frequently required 'follow-up' studies.

One kilogram of a pesticide is not necessarily equal to a kilogram of a different pesticide. This issue can be significant. Whether it is depends on the use to which pesticide-use data are put. While kilograms of pesticide is the most common way of measuring agricultural chemical use, the type of analysis will generally define what measure of chemical use is best. Quantifying the risk from the exposure to pesticides, for example, typically requires weighing usage or residues by acute or chronic health and environmental toxicity coefficients and subsequently estimating human or environmental exposure to such hazards. The interferences one draws concerning pesticide use can vary substantially depending on the measure considered.

Bis(acetato)amminedichloro(cyclohexylamine) platinum(IV) (JM216) is a new orally administered platinum complex with antitumor properties, and is currently undergoing phase II clinical trials. When JM216 was incubated with human plasma ultrafiltrate, 93% of the platinum species were protein-bound and 7% were unbound. The unbound platinum complexes in the ultrafiltrates of human plasma were analysed using a liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method. Apart from the parent drug, four metabolites were identified and characterised. These include JM118 [amminedichloro(cyclohexylamine) platinum(II)], JM383 [bis(acetato)ammine(cyclohexylamine)dihydroxo platinum(IV)] and the two isomers JM559 and JM518 [bis(acetato)amminechloro(cyclohexylamine) hydroxo platinum(IV)]. Their elemental compositions were determined by accurate mass measurement during the LC analysis, to confirm their identities. Quantitation of these metabolites by off-line LC atomic absorption spectroscopy demonstrated that JM118 is the major metabolite in plasma from patients receiving JM216 treatment.

In the evolution of mitral valve surgery, Ivalon sponge was sutured to the posterior leaflet of the mitral valve to obtain competency. Between August 1959 and October 1962, 18 patients had this procedure. All patients were discharged home. Three patients were lost to follow-up 5 to 10 years after operation. Valve replacement was necessary in 7 patients 10.4 +/- 8.5 years after repair. Bacterial endocarditis causing late death occurred in 5 patients within 4 years. Five embolic episodes occurred. The estimated probability of survival and need for valve replacement at 28 years were 29.2% +/- 12.3% and 12.4% +/- 6.7%, respectively.

Four patients have undergone heterotopic heart transplantation with donor hearts stored by a portable hypothermic perfusion system. Total ischemic periods ranged from 6 hours 55 minutes to 16 hours 50 minutes. One heart, transplanted into a patient who had acutely rejected a previous graft, suffered accelerated, irreversible, acute rejection within five days, associated with strong antibody formation; donor heart function was never good. In the 3 remaining patients, donor heart function was good after initially being poor for a few hours in 2 patients. One patient died of long-term rejection after 6 months and 1 of tuberculous meningitis after 10 months; 1 remains alive at 15 months. Neither preservation of the donor heart for periods in excess of approximately 4 hours nor the use of continuous hypothermic perfusion as a method of preservation appears to have been reported previously in the context of the clinical situation.

Traditional neo-Darwinian explanations for stasis involve limited variation, developmental constraints and stabilizing selection. Of these, stabilizing selection is regarded as the mechanism operating most widely. Arguments based on stabilizing selection, however, implicitly assume a one-way evolutionary relationship between organism and environment. In this paper, I suggest that stasis may arise in a number of different ways as a result of organism/environment coevolution. The chief causes of stasis may be the attainment of coadapted equilibria between organism and environment and periods of quiescence within and between arms races. I also suggest that many cases of stasis in the fossil records may be apparent rather than real due to a reliance on gross morphological trends and that apparently large environmental changes during which stasis persists may not reflect change in the coadapted components of the organisms' environment.

A procedure is described for matrix modification in the determination of metals in blood by flame spectrometric methods. The protein is removed by precipitation with dilute nitric acid and centrifugation and the supernatant liquid is used for direct analysis. Nitric acid is compared with other acids as the precipitant. The technique is simple, contamination-free and provides a solution which may be directly compared with aqueous calibration standards. Its application for determination of clinically important metals by flame atomic fluorescence and emission spectrometry is demonstrated.

This is a review of the last 307 patients with tetralogy of Fallot who were operated on in our unit at Groote Schuur Hospital and Red Cross War Memorial Children's Hospital. Complete repair was undertaken in 301 patients, and shunts were performed in 6 children. There were 17 hospital deaths and 1 late death. The mortality was 5.5% for children less than 12 years old and 6.6% in patients between 12 and 20 years old. During this study period, there was a change in our policy as to when complete repair should be attempted. At present, we perform systemic-pulmonary shunts in patients less than 6 months old and delay complete repair until the child is 2 years old. In deciding whether a shunt should precede complete repair, our experience has shown that age is not as important a consideration as the anatomy of the outflow tract of the right ventricle and pulmonary arteries.

Seven patients with heterotopic heart transplants have undergone further heart transplant procedures. In 5, the first heterotopically placed donor heart was excised and replaced with the second donor heart. In 2, the first heterotopic donor heart was left in situ and the patient's own heart (then nonfunctioning) was excised and replaced by the second donor heart; thus, these patients underwent orthotopic transplantation and were left with two donor hearts. The decision to perform retransplantation in a patient undergoing irreversible acute rejection is usually straightforward, but the timing of a further transplant procedure in a patient with advanced graft arteriosclerosis may present a difficult problem. Two of the 7 patients in this series died of infectious complications within the first 3 months after retransplantation. A third patient acutely rejected the second donor heart within 5 days, but survived an additional 17 months with the support of his own cardiomyopathic heart. Four patients remain alive and well between 5 and 36 months following the second transplant and between 17 and 54 months following the first transplant procedure.

The surgical technique of heterotopic heart transplantation is detailed and illustrated. The donor heart is excised after cardioplegic arrest and topical cooling; its preparation and implantation in the recipient are described. Emphasis is placed on ensuring nonrestrictive anastomoses between the left and right atria of the recipient and the donor, on estimating the optimal length of the donor aorta, and on the insertion of a prosthetic graft between the donor and the recipient pulmonary arteries. Forty-six such transplants have been performed to date without operative or early postoperative mortality related to technical problems.

The case of a Black African patient with an annular subvalvular left ventricular aneurysm of unknown origin is described, and the pathological findings in this condition together with a review of the literature is presented. We have operated on 12 patients with this condition between 1958 and 1978. Ventricular aneurysm in the Black African is extremely rare; aneurysms resulting from ischemic heart disease have not been encountered in this racial group, and contrary to earlier reports in the literature, syphilis is not the most common cause of left ventricular aneurysms in this group. The aneurysms arise in the fibrous rings below either the aortic or the mitral valve, extend around the valves in this situation, and may occur either singly or in both positions in the same heart. After various etiological factors are excluded, it is probable that in this group of patients the aneurysms develop initially as pulsion diverticula through a congenital weakness in the ventricular wall in the region of the atrioventricular groove.

A nonpulsatile perfusion apparatus, based on the air-lift pump principle, has been developed. Circulation of the perfusate, as well as oxygenation and maintenance of acid-base balance, is provided by the flow of a mixture of 97% oxygen and 3% carbon dioxide. The system is easily and entirely portable. Eleven baboons underwent orthotopic allotransplantation with donor hearts stored by continuous hypothermic (4-10 degrees C) perfusion for periods of up to 24 hr. Three were electively killed after 2 to 3 days; the remaining eight, immunosuppressed with methylprednisolone and either azathioprine or cyclosporin A, survived to rejection at between 10 and 49 days. Cardiac catheterization performed in six animals 7-14 days after allotransplantation showed virtually normal hemodynamic data. Three more baboons underwent heart excision and storage by hypothermic perfusion for 24 hr, and subsequent othotopic autotransplantation, the circulation of the baboon being maintained in the interim by an allograft. One animal survives 8 months later with hemodynamic data at cardiac catheterization differing little from that obtained before autotransplantation. This perfusion system has subsequently been used to store four human donor hearts prior to heterotopic transplantation.

An unusual but often lethal complication of mitral valve replacement is rupture of the left ventricle. The two recognized types of rupture are discussed, and the literature and pathology are reviewed. It is stressed that this complication can be prevented, and the factors involved in prevention are outlined.

A left ventricular bypass procedure using a cardiac allograft was performed in a patient with a long history of rheumatic heart disease and two aortic valve replacements. Normal cardiac function was reestablished, and the only problem following transplantation was that of serious arrhythmias involving the recipient heart. Eighteen months after left ventricular bypass bacterial endocarditis which was resistant to medical treatment developed on the aortic prosthesis. The patient underwent operation, the prosthesis was removed, and the recipient left ventricle was partially resected and excluded from the circulation. Since then the patient has been asymptomatic and, at the time of writing three years after cardiac allograft, he is our longest survivor.