Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.

Rethinking the consultation paradigm: Validity evidence for a new framework, a multimethods study.

BACKGROUND: In-hospital consultation is essential for patient care. We previously proposed a framework of seven specific consultation types to classify consult requests to improve communication, workflow, and provider satisfaction. METHODS: This multimethods study's aim was to evaluate the applicability of the consult classification framework to real internal medicine (IM) consults. We sought validity evidence using Kane's validity model with focus groups and classifying consult requests from five IM specialties. Participants attended five 1 h semi-structured focus groups that were recorded, transcribed, and coded for thematic saturation. For each specialty, three specialists and three hospitalists categorized 100 (total 500) random anonymized consult requests. The primary outcome was concordance in the classification of consult requests, defined as the sum of partial concordance and perfect concordance, where respectively 4-5/6 and 6/6 participants classified a consult in the same category. We used χ2 tests to compare concordance rates across specialties and between specialists and hospitalists. RESULTS: Five major themes were identified in the qualitative analysis of the focus groups: (1) consult question, (2) interpersonal interactions, (3) value, (4) miscommunication, (5) consult framework application, barriers, and iterative development. In the quantitative analysis, the overall concordance rate was 88.8% (95% confidence interval [CI]: 85.7-91.4), and perfect concordance was 46.6% (95% CI: 42.2-51.1). Concordance differed significantly between hospitalists and specialists overall (p = .01), with a higher proportion of hospitalists having perfect concordance compared to specialists (67.2% vs. 57.8%, p = .002). CONCLUSIONS: The consult classification framework was found to be applicable to consults from five different IM specialties, and could improve communication and education.

Comparison of direct oral anticoagulants versus low-molecular-weight heparin in primary and metastatic brain cancers: a meta-analysis and systematic review.

BACKGROUND: The safety and efficacy of direct-acting oral anticoagulants (DOACs) for therapeutic anticoagulation in the setting of primary or metastatic brain cancer is not known. OBJECTIVES: To conduct a meta-analysis and systematic review of studies that compare the risk of intracranial hemorrhage (ICH) in patients with brain cancer treated with DOACs vs low-molecular-weight heparin (LMWH). METHODS: A literature search was conducted using PubMed, EMBASE, and Cochrane databases. Summary statistics were obtained by calculating the risk ratio (RR), and heterogeneity across studies was estimated using the I2 statistic. A total of 10 retrospective studies (n = 1638) met criteria for inclusion. The primary endpoint was the pooled RR for ICH in patients with brain tumors receiving anticoagulation with DOACs compared with those receiving LMWH. Secondary analyses included the risk of fatal ICH in each subgroup. RESULTS: The pooled RR for ICH in patients receiving DOACs vs those receiving LMWH was 0.65 (95% CI, 0.36-1.17; P = .15; I2 = 50%). In studies evaluating primary brain cancer, there was a reduction in risk of ICH with DOACs (RR, 0.35; 95% CI, 0.18-0.69; P = .003; I2 = 0%). In patients with metastatic brain cancer, there was no difference in the risk of ICH with the type of anticoagulation (RR, 1.05; 95% CI, 0.71-1.56; P = .80; I2 = 0%). The overall risk of fatal ICH was not different between anticoagulants. CONCLUSION: The risk of ICH in patients with brain cancer receiving therapeutic anticoagulation varies by anticoagulation agent and diagnosis of primary or metastatic disease.

Anticoagulation management and related outcomes in patients with cancer-associated thrombosis and thrombocytopenia: A systematic review and meta-analysis.

BACKGROUND: Patients with cancer have an increased risk of both venous thromboembolism (VTE) requiring anticoagulation and thrombocytopenia. The optimal management is unclear. We performed a systematic review and meta-analysis to evaluate the outcomes in these patients. METHODS: We searched MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials from inception to February 5, 2022. Studies assessing adult patients with cancer-associated thrombosis and platelet count <100 × 109/L were included. Three anticoagulation management strategies were reported: full dose, modified dose, or no anticoagulation. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding. The incidence rates of thrombotic and bleeding outcomes by anticoagulation management strategies were descriptive, and were pooled using random effects model and expressed as events per 100 patient-months with associated 95 % confidence intervals (CI). RESULTS: We included 19 observational cohort studies (N = 1728 patients) in the systematic review, with 10 included in the meta-analysis (N = 707 patients). Approximately 90 % of patients had hematological malignancies, with low-molecular-weight heparin being the main anticoagulant. The rates of recurrent VTE and bleeding complications were high regardless of management strategies - recurrent VTE on full dose: 2.65/100 patient-months (95 % CI 1.62-4.32), modified dose: 3.51/100 patient-months (95 % CI 1.00-12.39); major bleeding on full dose: 4.45/100 patient-months (95 % CI 2.80-7.06), modified dose: 4.16/100 patient-months (95 % CI 2.24-7.74). There was serious risk of bias in all studies. CONCLUSIONS: Patients with cancer-associated thrombosis and thrombocytopenia have high risks of both recurrent VTE and major bleeding, but current literature is significantly limited to guide the best management.

Anticoagulation in cancer-associated thromboembolism with thrombocytopenia: a prospective, multicenter cohort study.

Venous thromboembolism (VTE) with concurrent thrombocytopenia is frequently encountered in patients with cancer. Therapeutic anticoagulation in the setting of thrombocytopenia is associated with a high risk of hemorrhage. Retrospective analyses suggest the utility of modified-dose anticoagulation in this population. To assess the incidence of hemorrhage or thrombosis according to anticoagulation strategy, we performed a prospective, multicenter, observational study. Patients with active malignancy, acute VTE, and concurrent thrombocytopenia (platelet count <100 000/µL) were enrolled. The cumulative incidences of hemorrhage or recurrent VTE were determined considering death as a competing risk. Primary outcomes were centrally adjudicated and comparisons made according to initial treatment with full-dose or modified-dose anticoagulation. A total of 121 patients were enrolled at 6 hospitals. Seventy-five patients were initially treated with full-dose anticoagulation (62%) and 33 (27%) with modified-dose anticoagulation; 13 (11%) patients received no anticoagulation. Most patients who received modified-dose anticoagulation had a hematologic malignancy (31 of 33 [94%]) and an acute deep vein thrombosis (28 of 33 [85%]). In patients who initially received full-dose anticoagulation, the cumulative incidence of major hemorrhage at 60 days was 12.8% (95% confidence interval [CI], 4.9-20.8) and 6.6% (95% CI, 2.4-15.7) in those who received modified-dose anticoagulation (Fine-Gray hazard ratio, 2.18; 95% CI, 1.21-3.93). The cumulative incidence of recurrent VTE at 60 days in patients who initially received full-dose anticoagulation was 5.6% (95% CI, 0.2-11) and 0% in patients who received modified-dose anticoagulation. In conclusion, modified-dose anticoagulation appears to be a safe alternative to therapeutic anticoagulation in patients with cancer who develop deep vein thrombosis in the setting of thrombocytopenia.

Intracranial hemorrhage with direct oral anticoagulants in patients with brain metastases.

Direct oral anticoagulants (DOACs) are increasingly prescribed in treatment of cancer-associated thrombosis, but limited data exist regarding safety of DOACs in patients with brain metastases. We aimed to determine the incidence of intracranial hemorrhage (ICH) in patients with brain metastases receiving DOACs or low-molecular-weight heparin (LMWH) for venous thromboembolism or atrial fibrillation. An international 2-center retrospective cohort study was designed. Follow-up started on the first day of concomitant anticoagulation and brain tumor diagnosis. At least 2 brain imaging studies were mandated. The primary outcome was the cumulative incidence of any spontaneous ICH at 12-month follow-up with death as a competing risk. Major ICH was defined as spontaneous, ≥10 mL in volume, symptomatic, or requiring surgical intervention. Imaging studies were centrally reviewed by a neuroradiologist blinded for anticoagulant type. PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke) score for prediction of ICH was calculated. We included 96 patients with brain metastases (41 DOAC, 55 LMWH). The 12-month cumulative incidence of major ICH was 5.1% in DOAC-treated patients and 11.1% in those treated with LMWH (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.09-2.21). When anticoagulation was analyzed as a time-varying covariate, the risk of any ICH did not differ between DOAC- and LMWH-treated patients (HR, 0.98; 95% CI, 0.28-3.40). PANWARDS score was not associated with ICH risk. This international 2-center study suggests comparable safety of LMWH and DOACs in patients with brain metastases.

Anticoagulation after intracranial hemorrhage in brain tumors: Risk of recurrent hemorrhage and venous thromboembolism.

BACKGROUND: Intracranial hemorrhage (ICH) is a common and often devastating outcome in patients with brain tumors. Despite this, there is little evidence to guide anticoagulation management following an initial ICH event. OBJECTIVES: To analyze the risk of recurrent hemorrhagic and thrombotic outcomes after an initial ICH event in patients with brain tumors and prior venous thromboembolism (VTE). PATIENTS AND METHODS: A retrospective cohort study was performed. Radiographic images obtained after initial ICH were reviewed for the primary outcomes of recurrent ICH and VTE. RESULTS AND CONCLUSIONS: A total of 79 patients with brain tumors who developed ICH on anticoagulation for VTE were analyzed. Fifty-four patients (68.4%) restarted anticoagulation following ICH. The cumulative incidence of recurrent ICH at 1 year was 6.1% (95% confidence interval [CI], 1.5-15.3) following reinitiation of anticoagulation. Following a major ICH (defined as an ICH >10 mL in size, causing symptoms, or requiring intervention), the rate of recurrent ICH upon reexposure to anticoagulation was 14.5% (95% CI, 2.1-38.35), whereas the rate of recurrent ICH following smaller ICH was 2.6% (95% CI, 0.2%-12.0%). Mortality following a recurrent ICH on anticoagulation was 67% at 30 days. The cumulative incidence of recurrent VTE was significantly lower in the restart cohort compared to patients who did not restart anticoagulation (8.1% vs 35.3%; P = .003). We conclude that resumption of anticoagulation is lowest among patients with metastatic brain tumors with small initial ICH. Following an initial major ICH, resumption of anticoagulation was associated with a high rate of recurrent ICH.

Lipopeptide biosurfactants from Paenibacillus polymyxa inhibit single and mixed species biofilms.

Although biofilms are recognised as important in microbial colonisation, solutions to their inhibition are predominantly based on planktonic assays. These solutions have limited efficacy against biofilms. Here, a series of biofilm-orientated tests were used to identify anti-biofilm compounds from marine micro-flora. This led to the isolation of a complex of anti-biofilm compounds from an extract of Paenibacillus polymyxa (PPE). A combination of rpHPLC and mass spectrometry identified the principle components of PPE as fusaricidin B (LI-FO4b) and polymyxin D1, with minor contributions from surfactins. This complex (PPE) reduced the biofilm biomass of Bacillus subtilis, Micrococcus luteus, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus bovis. In contrast, ampicillin was only effective against S. aureus. PPE also inhibited a self-assembling marine biofilm (SAMB) in co-incubation assays by 99.3% ± 1.9 and disrupted established SAMB by 72.4% ± 4.4, while ampicillin showed no significant reduction. The effectiveness of this complex of lipopeptides against single and multispecies biofilms suggests a future role in biofilm prevention strategies.

Association between implementation of a medical team training program and surgical morbidity.

OBJECTIVE: To determine whether there is an association between the Veterans Health Administration Medical Team Training (MTT) program and surgical morbidity. DESIGN, SETTING, AND PARTICIPANTS: A retrospective health services study was conducted with a contemporaneous control group. Outcome data were obtained from the Veterans Health Administration Surgical Quality Improvement Program. The analysis included aggregated measures representing 119,383 sampled procedures from 74 Veterans Health Administration facilities that provide care to veterans. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of change in annual surgical morbidity rate 1 year after facilities enrolled in the MTT program as compared with 1 year before and compared with the non-MTT program sites. RESULTS: Facilities in the MTT program (n = 42) had a significant decrease of 17% in observed annual surgical morbidity rate (rate ratio, 0.83; 95% CI, 0.79-0.88; P = .01). Facilities not trained (n = 32) had an insignificant decrease of 6% in observed morbidity (rate ratio, 0.94; 95% CI, 0.86-1.05; P = .11). After adjusting for surgical risk, we found a decrease of 15% in morbidity rate for facilities in the MTT program and a decrease of 10% for those not yet in the program. The risk-adjusted annual surgical morbidity rate declined in both groups, and the decline was 20% steeper in the MTT program group (P = .001) after propensity-score matching. The steeper decline in annual surgical morbidity rates was also observed in specific morbidity outcomes, such as surgical infection. CONCLUSION: The Veterans Health Administration MTT program is associated with decreased surgical morbidity.

Improving perceptions of teamwork climate with the Veterans Health Administration medical team training program.

There are differences between nurse and physician perceptions of teamwork. The purpose of this study was to determine whether these differences would be reduced with medical team training (MTT). The Safety Attitudes Questionnaire was administered to nurses and physicians working in the operating rooms of 101 consecutive hospitals before and at the completion of an MTT program. Responses to the 6 teamwork climate items on the Safety Attitudes Questionnaire were analyzed using nonparametric testing. At baseline, physicians had more favorable perceptions on teamwork climate items than nurses. Physicians demonstrated improvement on all 6 teamwork climate items. Nurses demonstrated improvement in perceptions on all teamwork climate items except "Nurse input is well received." Physicians still had a more favorable perception than nurses on all 6 teamwork climate items at follow-up. Despite an improvement in perceptions by physicians and nurses, baseline nurse-physician differences persisted at completion of the Veterans Health Administration MTT Program.

Incorrect surgical procedures within and outside of the operating room: a follow-up report.

OBJECTIVE: To describe incorrect surgical procedures reported from mid-2006 to 2009 from Veterans Health Administration medical centers and build on previously reported events from 2001 to mid-2006. DESIGN: Retrospective database review. SETTING: Veterans Health Administration medical centers. INTERVENTIONS: The Veterans Health Administration implemented Medical Team Training and continues to support their directive for ensuring correct surgery to improve surgical patient safety. MAIN OUTCOME MEASURES: The categories were incorrect procedure types (wrong patient, side, site, procedure, or implant), major or minor surgery, in or out of the operating room (OR), adverse event or close call, specialty, and harm. RESULTS: Our review produced 237 reports (101 adverse events, 136 close calls) and found decreased harm compared with the previous report. The rate of reported adverse events decreased from 3.21 to 2.4 per month (P = .02). Reported close calls increased from 1.97 to 3.24 per month (P ≤ .001). Adverse events were evenly split between OR (50) and non-OR (51). When in-OR events were examined as a rate, Neurosurgery had 1.56 and Ophthalmology had 1.06 reported adverse events per 10 000 cases. The most common root cause for adverse events was a lack of standardization of clinical processes (18%). CONCLUSIONS: The rate of reported adverse events and harm decreased, while reported close calls increased. Despite improvements, we aim to achieve further gains. Current plans and actions include sharing lessons learned from root cause analyses, policy changes based on root cause analysis review, and additional focused Medical Team Training as needed.

Changing perceptions of safety climate in the operating room with the Veterans Health Administration medical team training program.

Perceptions of organizational commitment to safety differ between the operating rooms in high- and medium-complexity facilities of the Veterans Health Administration (VHA). The purpose of this study was to see whether medical team training (MTT) reduced this difference. The Safety Attitudes Questionnaire was administered before and at the completion of a MTT program. The study population consisted of respondents working in the operating room. Responses to the 7 safety climate items were analyzed using nonparametric tests. Before MTT, respondents working at medium-complexity facilities had more favorable perceptions of knowledge of proper channels and encouragement by colleagues to report safety concerns than respondents who work at high-complexity facilities. At completion, there was no difference in perceptions between respondents working at high- and medium-complexity facilities for these items. The VHA MTT program improved perceptions at both high- and medium-complexity facilities and eliminated differences present at baseline.

Angiotensin-I-converting enzyme and prolyl endopeptidase inhibitory peptides from natural sources with a focus on marine processing by-products.

Like many natural resource-based processing industries, the seafood processing sector gives rise to a significant volume of organic waste. Environmental issues, economic concerns and legal restrictions regarding the disposal of processing wastes have led to increased research in the discovery of alternative value-added products, such as bioactive peptides from these waste streams. Bioactive peptides have various physiological functionalities in the human body following consumption and these include antihypertensive, antiamnesiac, mineral-binding, immunodulatory, antioxidative and antithrombotic activities. The search for bioactive peptides from a variety of different sources has become a major area of research with potential for the functional foods sector. The isolation of bioactive peptides typically involves the hydrolysis of the protein of choice with different proteolytic enzymes, alone or in combination with Generally Recognised as Safe (GRAS) micro-organisms. This review details information on angiotensin I-converting enzyme (ACE) and prolyl endopeptidase (PEP) inhibitors derived from natural, marine and marine processing waste streams and their potential for use as high-value added bioactive peptides.

Briefing guide study: preoperative briefing and postoperative debriefing checklists in the Veterans Health Administration medical team training program.

BACKGROUND: The purpose of this study was to examine the outcomes of checklist-driven preoperative briefings and postoperative debriefings during the Veterans Health Administration (VHA) medical team training program. METHODS: A briefing score (1, never started; 2, started then discontinued; 3, maintained on original targeted cases; 4, expanded to other services; 5, briefing all cases, all services) was established at 10.1 ± .3 months after introduction of the checklist. Outcomes included antibiotic and deep venous thrombosis prophylaxis compliance rates before and after use of the checklist. RESULTS: Antibiotic (97.0% ± .1% vs 92.1% ± 1.5%; P = .01) and deep venous thrombosis (95.7% ± .8% vs 85.1% ± 4.6%; P = .05) prophylaxis compliance rates were higher after initiation of a surgical checklist. CONCLUSIONS: Checklist-driven preoperative briefings and postoperative debriefings are associated with improvements in patient safety for surgical patients.

Association between implementation of a medical team training program and surgical mortality.

CONTEXT: There is insufficient information about the effectiveness of medical team training on surgical outcomes. The Veterans Health Administration (VHA) implemented a formalized medical team training program for operating room personnel on a national level. OBJECTIVE: To determine whether an association existed between the VHA Medical Team Training program and surgical outcomes. DESIGN, SETTING, AND PARTICIPANTS: A retrospective health services study with a contemporaneous control group was conducted. Outcome data were obtained from the VHA Surgical Quality Improvement Program (VASQIP) and from structured interviews in fiscal years 2006 to 2008. The analysis included 182,409 sampled procedures from 108 VHA facilities that provided care to veterans. The VHA's nationwide training program required briefings and debriefings in the operating room and included checklists as an integral part of this process. The training included 2 months of preparation, a 1-day conference, and 1 year of quarterly coaching interviews MAIN OUTCOME MEASURE: The rate of change in the mortality rate 1 year after facilities enrolled in the training program compared with the year before and with nontraining sites. RESULTS: The 74 facilities in the training program experienced an 18% reduction in annual mortality (rate ratio [RR], 0.82; 95% confidence interval [CI], 0.76-0.91; P = .01) compared with a 7% decrease among the 34 facilities that had not yet undergone training (RR, 0.93; 95% CI, 0.80-1.06; P = .59). The risk-adjusted mortality rates at baseline were 17 per 1000 procedures per year for the trained facilities and 15 per 1000 procedures per year for the nontrained facilities. At the end of the study, the rates were 14 per 1000 procedures per year for both groups. Propensity matching of the trained and nontrained groups demonstrated that the decline in the risk-adjusted surgical mortality rate was about 50% greater in the training group (RR,1.49; 95% CI, 1.10-2.07; P = .01) than in the nontraining group. A dose-response relationship for additional quarters of the training program was also demonstrated: for every quarter of the training program, a reduction of 0.5 deaths per 1000 procedures occurred (95% CI, 0.2-1.0; P = .001). CONCLUSION: Participation in the VHA Medical Team Training program was associated with lower surgical mortality.

The role of the operating room nurse manager in the successful implementation of preoperative briefings and postoperative debriefings in the VHA Medical Team Training Program.

To improve communication within surgical teams, Veterans Health Administration (VHA) implemented a Medical Team Training Program (MTT) based on the principles of crew resource management. One hundred two VHA facilities were analyzed. Nursing leadership participation in the planning stages of the program was compared with outcomes at follow-up. Nurse manager participation in planning was associated with higher rates of implementation of preoperative briefing and postoperative debriefing. Nurse managers are a critical component in the planning phase of team training programs focused on OR clinical staff.

Medical team training and coaching in the Veterans Health Administration; assessment and impact on the first 32 facilities in the programme.

BACKGROUND: Communication is problematic in healthcare. The Veterans Health Administration is implementing Medical Team Training. The authors describe results of the first 32 of 130 sites to undergo the programme. This report is unique; it provides aggregate results of a crew resource-management programme for numerous facilities. METHODS: Facilities were taught medical team training and implemented briefings, debriefings and other projects. The authors coached teams through consultative phone interviews over a year. Implementation teams self-reported implementation and rated programme impact: 1='no impact' and 5='significant impact.' We used logistic regression to examine implementation of briefing/debriefing. RESULTS: Ninety-seven per cent of facilities implemented briefings and debriefings, and all implemented an additional project. As of the final interview, 73% of OR and 67% of ICU implementation teams self-reported and rated staff impact 4-5. Eighty-six per cent of OR and 82% of ICU implementation teams self-reported and rated patient impact 4-5. Improved teamwork was reported by 84% of OR and 75% of ICU implementation teams. Efficiency improvements were reported by 94% of OR implementation teams. Almost all facilities (97%) reported a success story or avoiding an undesirable event. Sites with lower volume were more likely to conduct briefings/debriefings in all cases for all surgical services (p=0.03). CONCLUSIONS: Sites are implementing the programme with a positive impact on patients and staff, and improving teamwork, efficiency and safety. A unique feature of the programme is that implementation was facilitated through follow-up support. This may have contributed to the early success of the programme.

Differences in nurse and surgeon perceptions of teamwork: implications for use of a briefing checklist in the OR.

The quality of teamwork among health care professionals is known to affect patient outcomes. In the OR, surgeons report more favorable perceptions of communication during procedures and of teamwork effectiveness than do nurses. We undertook a quality improvement project in the Veterans Health Administration to confirm reported teamwork differences between perioperative nurses and surgeons and to examine the implications of these differences for improving practice patterns in the OR. The Safety Attitudes Questionnaire, which measures safety culture, including the quality of communication and collaboration among health care providers who routinely work together, was administered in 34 hospitals. Perioperative nurses who participated in the survey rated teamwork higher with other nurses than with surgeons, but surgeons rated teamwork high with each other and with nurses. On five of six communication and collaboration items, surgeons had a significantly more favorable perception than did perioperative nurses. To increase the likelihood of success when implementing the use of checklist-based crew resource management tools, such as the World Health Organization's Surgical Safety Checklist, project leaders should anticipate differences in perception between members of the different professions that must be overcome if teamwork is to be improved.