Pre-emptive intraoperative administration of PCC4 in cardiac surgery patients at high risk of bleeding: A pilot study.

BACKGROUND: Four-factor prothrombin complex (PCC4), a concentrate of factors II, VII, IX, and X and proteins C and S, has been used selectively for reversal of oral anticoagulation before surgery. There is data to support PCC4 as opposed to supplemental fresh frozen plasma (FFP) to manage postoperative bleeding following cardiac surgery. The preemptive, intraoperative use of PCC4 in cardiothoracic surgery has not been studied though it may prevent postoperative bleeding, the need for blood transfusion and the risk of transfusion-related acute lung injury, volume overload, and right ventricular (RV) heart failure. The purpose of this study is to evaluate the intraoperative administration of PCC4 to decrease bleeding and lower the rate of blood transfusion. METHODS: A single institution retrospective chart review was conducted from May 2020 to November 2021 of patients who received PCC4 intraoperatively during cardiothoracic surgery of high-risk variety. Patients were evaluated for the type of surgery, demographics, baseline anticoagulation, PCC4 dose, type and quantity of blood transfusion within 72 hours (h) postoperatively, chest tube output, the incidence of RV failure, hypersensitivity reactions, acute kidney injury (AKI), thrombosis, acute lung injury, and mortality within 45 days of the operative dose of PCC4. RESULTS: Thirty-five patients received PCC4 at a mean dose of 2920 units (U). Sixty-five percent of cases were left ventricular assist devices (LVADs) or heart transplants. The protocol is to use PCC4 30 units (U)/kg immediately after the completion of protamine administration. Inclusion criteria are cardiothoracic surgery with increased risk of postoperative right heart failure commonly secondary to blood product transfusion, or cardiothoracic surgery associated with increased risk of bleeding, including heart transplant, LVAD implant, aortic dissection, and redo sternotomy (e.g., coronary artery bypass). Total chest tube output was recorded as a mean of 757 ml for 24 h after surgery (32 ml/h). Overall median event rates of FFP and red blood cell (RBC) transfusions were 0 (interquartile range [IQR]: 0-3 U) and 4 (IQR: 2-5 U). Overall, 43% and 89% of cases received FFP and RBC, respectively. There was one occurrence of RV failure, one occurrence of AKI requiring renal replacement therapy, one occurrence of venoarterial extracorporeal membrane oxygenation, one occurrence of venous thromboembolism related to a central venous access line, and one death unrelated to surgery or PCC4 that was attributed to advanced heart failure not amenable to advanced therapies. CONCLUSION: Overall patients received a low rate of blood transfusion, had minimal chest tube output, and there was a small incidence of right heart failure. Patients did not have an increased risk of adverse effects such as AKI or venous thromboembolism. A randomized controlled clinical trial comparing the observed dose and timing of PCC4 versus routine postoperative bleeding management with blood product transfusion is recommended.

ProPACC: Protocol for a Trial of Integrated Specialty Palliative Care for Critically Ill Older Adults.

BACKGROUND: Each year, approximately one million older adults die in American intensive care units (ICUs) or survive with significant functional impairment. Inadequate symptom management, surrogates' psychological distress and inappropriate healthcare use are major concerns. Pioneering work by Dr. J. Randall Curtis paved the way for integrating palliative care (PC) specialists to address these needs, but convincing proof of efficacy has not yet been demonstrated. DESIGN: We will conduct a multicenter patient-randomized efficacy trial of integrated specialty PC (SPC) vs. usual care for 500 high-risk ICU patients over age 60 and their surrogate decision-makers from five hospitals in Pennsylvania. INTERVENTION: The intervention will follow recommended best practices for inpatient PC consultation. Patients will receive care from a multidisciplinary SPC team within 24 hours of enrollment that continues until hospital discharge or death. SPC clinicians will meet with patients, families, and the ICU team every weekday. SPC and ICU clinicians will jointly participate in proactive family meetings according to a predefined schedule. Patients in the control arm will receive routine ICU care. OUTCOMES: Our primary outcome is patient-centeredness of care, measured using the modified Patient Perceived Patient-Centeredness of Care scale. Secondary outcomes include surrogates' psychological symptom burden and health resource utilization. Other outcomes include patient survival, as well as interprofessional collaboration. We will also conduct prespecified subgroup analyses using variables such as PC needs, measured by the Needs of Social Nature, Existential Concerns, Symptoms, and Therapeutic Interaction scale. CONCLUSIONS: This trial will provide robust evidence about the impact of integrating SPC with critical care on patient, family, and health system outcomes.

A Pilot Randomized Trial of an Interactive Web-based Tool to Support Surrogate Decision Makers in the Intensive Care Unit.

Rationale: Breakdowns in clinician-family communication in intensive care units (ICUs) are common, yet there are no easily scaled interventions to prevent this problem.Objectives: To assess the feasibility, usability, acceptability, and perceived effectiveness of a communication intervention that pairs proactive family meetings with an interactive, web-based tool to help surrogates prepare for clinician-family meetings.Methods: We conducted a two-arm, single-blind, patient-level randomized trial comparing the Family Support Tool with enhanced usual care in two ICUs in a tertiary-care hospital. Eligible participants included surrogates of incapacitated patients judged by their physicians to have ≥40% risk of death or severe long-term functional impairment. The intervention group received unlimited tool access, with prompts to complete specific content upon enrollment and before two scheduled family meetings. Before family meetings, research staff shared with clinicians a one-page summary of surrogates' main questions, prognostic expectations, beliefs about the patient's values, and attitudes about goals of care. The comparator group received usual care enhanced with scheduled family meetings. Feasibility outcomes included the proportion of participants who accessed the tool before the first family meeting, mean number of logins, and average tool engagement time. We assessed tool usability with the System Usability Scale, assessed tool acceptability and perceived effectiveness with internally developed questionnaires, and assessed quality of communication and shared decision-making using the Quality of Communication questionnaire.Results: Of 182 screened patients, 77 were eligible. We enrolled 52 (67.5%) patients and their primary surrogate. Ninety-six percent of intervention surrogates (24/25) accessed the tool before the first family meeting (mean engagement time, 62 min ± 27.7) and logged in 4.2 times (±2.1) on average throughout the hospitalization. Surrogates reported that the tool was highly usable (mean, 82.4/100), acceptable (mean, 4.5/5 ± 0.9), and effective (mean, 4.4/5 ± 0.2). Compared with the control group, surrogates who used the tool reported higher overall quality of communication (mean, 8.9/10 ± 1.6 vs. 8.0/10 ± 2.4) and higher quality in shared decision-making (mean, 8.7/10 ± 1.5 vs. 8.0/10 ± 2.4), but the difference did not reach statistical significance.Conclusions: It is feasible to deploy an interactive web-based tool to support communication and shared decision-making for surrogates in ICUs. Surrogates and clinicians rated the tool as highly usable, acceptable, and effective.

Physical examination of the female cancer patient with sexual concerns: What oncologists and patients should expect from consultation with a specialist.

Answer questions and earn CME/CNE Sexual concerns are prevalent in women with cancer or cancer history and are a factor in patient decision making about cancer treatment and risk-reduction options. Physical examination of the female cancer patient with sexual concerns, regardless of the type or site of her cancer, is an essential and early component of a comprehensive evaluation and effective treatment plan. Specialized practices are emerging that focus specifically on evaluation and treatment of women with cancer and sexual function problems. As part of a specialized evaluation, oncologists and their patients should expect a thorough physical examination to identify or rule out physical causes of sexual problems or dysfunction. This review provides oncology professionals with a description of the physical examination of the female cancer patient with sexual function concerns. This description aims to inform anticipatory guidance for the patient and to assist in interpreting specialists' findings and recommendations. In centers or regions where specialized care is not yet available, this review can also be used by oncology practices to educate and support health care providers interested in expanding their practices to treat women with cancer and sexual function concerns. CA Cancer J Clin 2016;66:241-263. © 2016 American Cancer Society.

Evaluating the Use of Bortezomib and Eculizumab in Desensitization of Transplant Patients.

Objective: To systematically review the existing literature concerning the utilization of bortezomib and eculizumab to determine if there is enough evidence to warrant their routine use in desensitization protocols for high-risk transplant candidates. Data Sources: PubMed, Google Scholar, and ClinicalTrials.gov were searched using the terms bortezomib, eculizumab, desensitization, transplant, highly-sensitized, pre-sensitized, and antibody-mediated rejection (AMR). The articles included were published between January 2009 and August 2012. Study Selection and Data Extraction: All English-language articles involving human subjects were assessed for inclusion. The search included articles evaluating the use of these agents in desensitization and the prevention of AMR, but excluded articles investigating these drugs in the treatment of established AMR. Data Synthesis: Highly sensitized transplant candidates are at an increased risk of developing AMR after transplant; desensitization potentially reduces this risk. The addition of bortezomib and eculizumab to current desensitization protocols may enhance outcomes. The bortezomib search produced 3 efficacy trials, 1 safety trial, 2 in-progress trials, 14 patient cases from 8 published case reports, and 3 efficacy study abstracts. Conclusions: Much of the available literature assessing the efficacy of bortezomib and eculizumab for use in desensitization exists as restricted clinical trials and incomplete case reports. Bortezomib and eculizumab appear to be potentially effective additions to current desensitization protocols. However, we are unable to determine at this time whether these agents improve the most clinically relevant outcome of successful transplantation. Further well-designed clinical trials are needed to determine their true clinical efficacy in highly sensitized transplant candidates.

Behavioral couples therapy for the treatment of substance abuse: a substantive and methodological review of O'Farrell, Fals-Stewart, and colleagues' program of research.

Behavioral couples therapy (BCT) is an evidence-based couple therapy intervention for married or cohabitating substance abusers and their partners. This paper provides readers with a substantive and methodological review of Fals-Stewart, O'Farrell, and colleagues' program of research on BCT. The 23 studies included in this review provide support for the efficacy of BCT for improving substance use behavior, dyadic adjustment, child psychosocial outcomes, and reducing partner violence. This review includes a description of BCT, summaries of primary and secondary outcomes, highlights methodological strengths and weaknesses, notes barriers to dissemination, suggests future research directions, and provides clinical implications for couple and family therapists. Although there are several versions of BCT developed for the treatment of substance abuse this paper focuses on the version developed by O'Farrell, Fals-Stewart, and colleagues.

Family influences on adolescent gambling behavior: a review of the literature.

Gambling, and gambling related problems, are recognized as an emerging health issue among adolescents. Adolescent gambling is associated with numerous individual, social, and family characteristics. This paper provides a review of 21 empirical studies published between 1997 and 2008 that examine family influences on adolescent gambling behavior. Family influences on gambling behavior are conceptualized in the following five domains: (1) family sociodemographic factors, (2) general family climate, (3) family members' attitudes and behaviors, (4) parenting practices, and (5) family relationship characteristics. Based on the review of extant literature, there is empirical evidence that family characteristics are associated with adolescent gambling and further examination of family system influences on gambling behavior is needed. Gaps in the current literature and recommendations for future research are discussed to help inform the study of family influences on adolescent gambling behavior.

Conceptualizing and treating problem gambling as a family issue.

Few family therapists have training in the identification, assessment, and treatment of problem gambling and its impact on couple and family relationships. The authors conceptualize problem gambling (PG) as a family issue and encourage clinicians and researchers to pay attention to the systemic antecedents and consequences of PG on family relationships. A review of the literature and clinicians' experiences regarding the impact of PG on couple and family relationships are presented and discussed. In light of the limited systemic-based treatments for PG, marriage and family therapists are urged to begin paying attention to this emerging issue that has significant couple and family ramifications.

CX3CL1 up-regulation is associated with recruitment of CX3CR1+ mononuclear phagocytes and T lymphocytes in the lungs during cigarette smoke-induced emphysema.

CX3CR1 is expressed on monocytes, dendritic cells, macrophages, subsets of T lymphocytes, and natural killer cells and functions in diverse capacities such as leukocyte adhesion, migration, and cell survival on ligand binding. Expression of the CX3CL1 gene, whose expression product is the sole ligand for CX3CR1, is up-regulated in human lungs with chronic cigarette smoke-induced obstructive lung disease. At present, it is unknown whether CX3CL1 up-regulation is associated with the recruitment and accumulation of immune cells that express CX3CR1. We show that mice chronically exposed to cigarette smoke up-regulate CX3CL1 gene expression, which is associated with an influx of CX3CR1+ cells in the lungs. The increase in CX3CR1+ cells is primarily comprised of macrophages and T lymphocytes and is associated with the development of emphysema. In alveolar macrophages, cigarette smoke exposure increased the expression of both CX3CR1 and CX3CL1 genes. The inducibility of CX3CR1 expression was not solely dependent on a chronic stimulus because lipopolysaccharide up-regulated CX3CR1 in RAW264.7 cells in vitro and in mononuclear phagocytes in vivo. Our findings suggest a mechanism by which macrophages amplify and promote CX3CR1+ cell accumulation within the lungs during both acute and chronic inflammatory stress. We suggest that one function of the CX3CR1-CX3CL1 pathway is to recruit and sustain divergent immune cell populations implicated in the pathogenesis of cigarette smoke-induced emphysema.

Quambalaria species, including Q. coyrecup sp. nov., implicated in canker and shoot blight diseases causing decline of Corymbia species in the southwest of Western Australia.

A severe canker disease has been causing decline and death of Corymbia calophylla in the southwest of Western Australia (WA) for some years, but the causal agent has never been investigated. However, there have been historical reports dating back to the 1920s of a canker disease of amenity planted C. ficifolia caused by 'Sporotrichum destructor', though the description and Latin diagnosis were never published. It has been suggested that there may be links between this species and the genus Quambalaria, a group containing leaf and shoot pathogens of species of Eucalyptus and Corymbia. The aim of this study was to investigate the identity of the pathogen historically attributed to canker disease of C. ficifolia, determine whether this pathogen is responsible for the current epidemic of C. calophylla canker, and whether it is synonymous with Quambalaria. Surveys examined the range of Quambalaria spp. on Corymbia spp. endemic to southwest WA. Their phylogenetic relationship to Q. cyanescens, Q. eucalypti, and Q. pitereka was examined using rLSU and ITS sequence data. Morphological characters were also compared. Sequences confirmed that Q. cyanescens and Q. pitereka are present in southwest WA, with the latter associated with leaf and shoot disease. A third group isolated from cankers represent a new species of Quambalaria. Comparisons of disease symptoms and conidiogenesis indicate this species is synonymous with 'S. destructor'. The species is formally described here as Q. coyrecup sp. nov.