Fibrinogen levels in severe trauma: A preliminary comparison of Clauss Fibrinogen, ROTEM Sigma, ROTEM Delta and TEG 6s assays from the FEISTY pilot randomised clinical trial.

OBJECTIVE: To describe the relationships between different methods of measuring functional fibrinogen levels in severely injured, bleeding trauma patients across multiple timepoints during hospitalisation. METHODS: In 100 adult trauma patients enrolled in the FEISTY pilot randomised clinical trial at four tertiary trauma centres in Australia, blood samples were collected prospectively. Consistency of agreement was calculated, comparing functional fibrinogen levels measured by four methods - ROTEM® Delta and Sigma FIBTEM A5, TEG® 6s CFF MA, and gold-standard Clauss Fibrinogen. RESULTS: Comparing the ROTEM® Delta and new-generation ROTEM® Sigma machine, consistency of agreement for FIBTEM A5, measured by calculating intraclass correlation coefficients (ICCs), was ≥0.73 across all analysed timepoints, with mean differences (Sigma minus Delta) of 0.10-3.57 mm. Corresponding values comparing the ROTEM® Sigma FIBTEM A5 and TEG® 6s CFF MA were ICC = 0.55-0.82 and ICC = 4.69-7.97 (CFF MA minus A5). Comparing ROTEM® Sigma FIBTEM A5 and Clauss Fibrinogen Analysis (CFA), among statistically significant simple linear regression models, R2 was 0.25-0.67, and comparing TEG® 6s CFF MA and CFA (CFA) 0.65-0.82, although not all differences were significant with the latter comparison. Relationships across all timepoints combined were Clauss Fibrinogen (CF) (g/L) = 0.21𝑥 + 0.004 (where 𝑥 = ROTEM® Sigma FIBTEM A5 in mm) and (g/L) = 0.16𝑥 - 0.06 (where 𝑥 = TEG® 6s CFF MA in mm). CONCLUSIONS: The present study revealed acceptable agreement between four different assays measuring functional fibrinogen, with current- and previous-generation ROTEM® machines (Sigma, Delta) performing similarly measuring functional fibrinogen via FIBTEM assay. This suggests that haemostatic resuscitation algorithms designed for the ROTEM® Delta can be applied to the ROTEM® Sigma to guide fibrinogen replacement.

Hemostatic Profiles of Patients Who Underwent Transcatheter Versus Surgical Aortic Valve Replacement Versus Percutaneous Coronary Intervention.

Guidelines for transcatheter aortic valve replacement (TAVR) antithrombotic prophylaxis are extrapolated predominantly from percutaneous coronary intervention (PCI) data. Here, we examined temporal coagulation changes occurring in the early perioperative period to determine the pathobiologic validity of this supposition. This was a prospective observational study of consecutive patients who underwent transfemoral TAVR (n = 27), PCI (n = 12), or surgical aortic valve replacement (SAVR) requiring cardiopulmonary bypass and cross-clamping (n = 12). Blood samples were taken at 4 time points: T1 (baseline), after general anesthesia or sedation; T2, after heparin administration; T3, at the end of the procedure; and T4, 6 hours after the procedure. The samples were assessed concurrently using standard laboratory coagulation tests and viscoelastic tests of whole blood clotting, including the latest generation thromboelastometry (ROTEM sigma) and thromboelastometry (TEG 6s). Patients in the TAVR cohort were older and a had lower baseline hemoglobin level than patients in the PCI and SAVR cohorts. The baseline platelet function was similar between the TAVR and PCI cohorts and impaired in the SAVR cohort Figure S1. The baseline hemostatic measures were comparable among cohorts. Regarding the per-patient change from baseline, the TAVR cohort showed an overall more prothrombotic state than the other cohorts, with the most marked differences from the SAVR cohort after intraoperative heparin administration and from the PCI cohorts 6 hours after the procedure. In addition, the ROTEM and TEG parameters were well correlated but not interchangeable. In conclusion, patients who underwent TAVR have a more prothrombotic hemostatic profile than PCI and SAVR patients. These findings question the current guidelines that extrapolate antithrombotic regimens from PCI to TAVR settings.

Sepsis-associated acute kidney injury in the intensive care unit: incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes. A multicenter, observational study.

PURPOSE: The Acute Disease Quality Initiative (ADQI) Workgroup recently released a consensus definition of sepsis-associated acute kidney injury (SA-AKI), combining Sepsis-3 and Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria. This study aims to describe the epidemiology of SA-AKI. METHODS: This is a retrospective cohort study carried out in 12 intensive care units (ICUs) from 2015 to 2021. We studied the incidence, patient characteristics, timing, trajectory, treatment, and associated outcomes of SA-AKI based on the ADQI definition. RESULTS: Out of 84,528 admissions, 13,451 met the SA-AKI criteria with its incidence peaking at 18% in 2021. SA-AKI patients were typically admitted from home via the emergency department (ED) with a median time to SA-AKI diagnosis of 1 day (interquartile range (IQR) 1-1) from ICU admission. At diagnosis, most SA-AKI patients (54%) had a stage 1 AKI, mostly due to the low urinary output (UO) criterion only (65%). Compared to diagnosis by creatinine alone, or by both UO and creatinine criteria, patients diagnosed by UO alone had lower renal replacement therapy (RRT) requirements (2.8% vs 18% vs 50%; p < 0.001), which was consistent across all stages of AKI. SA-AKI hospital mortality was 18% and SA-AKI was independently associated with increased mortality. In SA-AKI, diagnosis by low UO only, compared to creatinine alone or to both UO and creatinine criteria, carried an odds ratio of 0.34 (95% confidence interval (CI) 0.32-0.36) for mortality. CONCLUSION: SA-AKI occurs in 1 in 6 ICU patients, is diagnosed on day 1 and carries significant morbidity and mortality risk with patients mostly admitted from home via the ED. However, most SA-AKI is stage 1 and mostly due to low UO, which carries much lower risk than diagnosis by other criteria.

Rotational thromboelastometry values across age groups in all trauma patients presenting to a level 1 trauma centre: An observational study.

OBJECTIVES: To describe rotational thromboelastometry (ROTEM) values (FIBTEM A5, EXTEM A5 and EXTEM CT) across age groups and assess for a statistical trend; and to determine whether any trend in ROTEM values is affected by severity of injury and packed red blood cells (PRBC) requirement. METHODS: Retrospective observational study at a level 1 trauma centre in Queensland, Australia. A total of 1601 consecutive trauma patients presenting to the ED. ROTEM data described included FIBTEM A5, EXTEM A5 and EXTEM CT. These values are described by age group (≤30 years, 31-45 years, 46-60 years, 61-75 years and >75 years), Injury Severity Score (ISS) category (<12, ≥12, <25 and ≥25) and number of PRBCs transfused in the first 24 h of admission (0 units, 1-4 units, 5-9 units and ≥10 units). RESULTS: The median age of participants was 37 years (interquartile range [IQR] 25-54 years), with 48.2% of patients had severe trauma (ISS >12) and 13.2% receiving at least one unit of PRBC in the first 24 h of admission. Median (IQR) values for FIBTEM A5, EXTEM A5 and EXTEM CT were 13 mm (10-16 mm), 45 mm (40-49 mm) and 62 s (56-71 s), respectively. A test for trend over progressive age groups showed an increase in FIBTEM A5 (P < 0.001) and EXTEM A5 values (P < 0.001) and a decrease in EXTEM CT values (P < 0.001). CONCLUSION: The present study demonstrated a pattern of increasing coagulability, as defined by ROTEM, with increasing age group in trauma patients, even among the severely injured. Further investigation is required to determine the clinical impact of these findings on both the ROTEM-guided management and longitudinal outcomes of these patients and whether an age-specific approach is beneficial.

Venoarterial extracorporeal membrane oxygenation for cardiac support in human immunodeficiency virus-positive patients: a case report and review of a multicentre registry.

BACKGROUND: Human immunodeficiency virus (HIV) is associated with increased risk of heart failure via multiple mechanisms both in patients with and without access to highly active antiretroviral therapy (HAART). Limited information is available on outcomes among this population supported on Venoarterial Extracorporeal Membrane Oxygenation (VA ECMO), a form of temporary mechanical circulatory support. METHODS: We aimed to assess outcomes and complications among patients with HIV supported on VA ECMO reported to a multicentre registry and present a case report of a 32 year old male requiring VA ECMO for cardiogenic shock as a consequence of his untreated HIV and acquired immune deficiency syndrome (AIDS). A retrospective analysis of the Extracorporeal Life Support Organization (ELSO) registry data from 1989 to 2019 was performed in HIV patients supported on VA ECMO. RESULTS: 36 HIV positive patients were reported to the ELSO Database who received VA ECMO during the study period with known outcomes. 15 patients (41%) survived to discharge. No significant differences existed between survivors and non-survivors in demographic variables, duration of VA ECMO support or cardiac parameters. Inotrope and/or vasopressor requirement prior to or during VA ECMO support was associated with increased mortality. Survivors were more likely to develop circuit thrombosis. The patient presented was supported on VA ECMO for 14 days and was discharged from hospital day 85. CONCLUSIONS: A limited number of patients with HIV have been supported with VA ECMO and more data is required to ascertain the indications for ECMO in this population. HIV should not be considered an absolute contraindication to VA ECMO as they may have comparable outcomes to other patient groups requiring VA ECMO support.

PREdiction and Diagnosis using Imaging and Clinical biomarkers Trial in Traumatic Brain Injury (PREDICT-TBI) study protocol: an observational, prospective, multicentre cohort study for the prediction of outcome in moderate-to-severe TBI.

INTRODUCTION: Traumatic brain injury (TBI) is a heterogeneous condition with a broad spectrum of injury severity, pathophysiological processes and variable outcomes. For moderate-to-severe TBI survivors, recovery is often protracted and outcomes can range from total dependence to full recovery. Despite advances in medical treatment options, prognosis remains largely unchanged. The objective of this study is to develop a machine learning predictive model for neurological outcomes at 6 months in patients with a moderate-to-severe TBI, incorporating longitudinal clinical, multimodal neuroimaging and blood biomarker predictor variables. METHODS AND ANALYSIS: A prospective, observational, cohort study will enrol 300 patients with moderate-to-severe TBI from seven Australian hospitals over 3 years. Candidate predictors including demographic and general health variables, and longitudinal clinical, neuroimaging (CT and MRI), blood biomarker and patient-reported outcome measures will be collected at multiple time points within the acute phase of injury. The predictor variables will populate novel machine learning models to predict the Glasgow Outcome Scale Extended 6 months after injury. The study will also expand on current prognostic models by including novel blood biomarkers (circulating cell-free DNA), and the results of quantitative neuroimaging such as Quantitative Susceptibility Mapping and Dynamic Contrast Enhanced MRI as predictor variables. ETHICS AND DISSEMINATION: Ethical approval has been obtained by the Royal Brisbane and Women's Hospital Human Research Ethics Committee, Queensland. Participants or their substitute decision-maker/s will receive oral and written information about the study before providing written informed consent. Study findings will be disseminated by peer-review publications and presented at national and international conferences and clinical networks. TRIAL REGISTRATION NUMBER: ACTRN12620001360909.

Substitution of ROTEM FIBTEM A5 for A10 in trauma: an observational study building a case for more rapid analysis of coagulopathy.

PURPOSE: Rotational thromboelastometry (ROTEM®) allows guided blood product resuscitation to correct trauma-induced coagulopathy in bleeding trauma patients. FIBTEM amplitude at 10 min (A10) has been widely used to identify hypofibrinogenaemia; locally a threshold of < 11 mm has guided fibrinogen replacement. Amplitude at 5 min (A5) carries an inherent time advantage. The primary aim was to explore the relationship between FIBTEM A5 and A10 in a trauma. Secondary aim was to investigate the use of A5 as a surrogate for A10 within a fibrinogen-replacement algorithm. METHODS: Retrospective observational cohort study of arrival ROTEM results from 1539 consecutive trauma patients at a Level 1 trauma centre in Australia. Consistency of agreement between FIBTEM A5 and A10 was assessed. A new fibrinogen replacement threshold was developed for A5 using the A5-A10 bias; this was clinically compared to the existing A10 threshold. RESULTS: FIBTEM A5 displayed excellent consistency of agreement with A10. Intraclass correlation coefficient = 0.972 (95% confidence interval [CI] 0.969-0.974). Bias of A5 to A10 was - 1.49 (95% CI 1.43-1.56) mm. 19.34% patients met the original local threshold of A10 < 11 mm; 19.28% patients met the new, bias-adjusted threshold of A5 < 10 mm. CONCLUSION: ROTEM FIBTEM A5 reliably predicts A10 in trauma. This further validates use of the A5 result over A10 allowing faster decision-making in time-critical resuscitation of trauma patients. A modification of -1 to the A10 threshold might be appropriate for use with the A5 value in trauma patients.

Fluid resuscitation after cardiac surgery in the intensive care unit: A bi-national survey of clinician practice. (The FRACS-ICU clinician survey).

Context and Aims: To describe current fluid and vasopressor practices after cardiac surgery in Australia and New Zealand cardiothoracic intensive care units (ICU). Design and Setting: This web-based survey was conducted in cardiothoracic ICUs in Australia and New Zealand. Methods: Intensivists, cardiac surgeons, and anesthetists were contacted to complete the online survey that asked questions regarding first and second choice fluids and vasopressors and the tools and factors that influenced these choices. Results: There were 96 respondents including 51 intensivists, 27 anesthetists, and 18 cardiac surgeons. Balanced crystalloids were the most preferred fluids (70%) followed by 4% albumin (18%) overall and among intensivists and anesthetists; however, cardiac surgeons (41%) preferred 4% albumin as their first choice. The most preferred second choice was 4% albumin (74%). Among vasopressors, noradrenaline was the preferred first choice (93%) and vasopressin the preferred second choice (80%). 53% initiated blood transfusion at a hemoglobin threshold of 70 g/L. Clinical acumen and mean arterial pressure were the most commonly used modalities in determining the need for fluids. Conclusions: There is practice variation in preference for fluids used in cardiac surgical patients in Australia and New Zealand; however, balanced crystalloids and 4% albumin were the most popular choices. In contrast, there is broad agreement with the use of noradrenaline and vasopressin as first and second-line vasopressors. These data will inform the design of future studies that aim to investigate hemodynamic management post cardiac surgery.

Derivation and validation of a machine learning risk score using biomarker and electronic patient data to predict progression of diabetic kidney disease.

AIM: Predicting progression in diabetic kidney disease (DKD) is critical to improving outcomes. We sought to develop/validate a machine-learned, prognostic risk score (KidneyIntelX™) combining electronic health records (EHR) and biomarkers. METHODS: This is an observational cohort study of patients with prevalent DKD/banked plasma from two EHR-linked biobanks. A random forest model was trained, and performance (AUC, positive and negative predictive values [PPV/NPV], and net reclassification index [NRI]) was compared with that of a clinical model and Kidney Disease: Improving Global Outcomes (KDIGO) categories for predicting a composite outcome of eGFR decline of ≥5 ml/min per year, ≥40% sustained decline, or kidney failure within 5 years. RESULTS: In 1146 patients, the median age was 63 years, 51% were female, the baseline eGFR was 54 ml min-1 [1.73 m]-2, the urine albumin to creatinine ratio (uACR) was 6.9 mg/mmol, follow-up was 4.3 years and 21% had the composite endpoint. On cross-validation in derivation (n = 686), KidneyIntelX had an AUC of 0.77 (95% CI 0.74, 0.79). In validation (n = 460), the AUC was 0.77 (95% CI 0.76, 0.79). By comparison, the AUC for the clinical model was 0.62 (95% CI 0.61, 0.63) in derivation and 0.61 (95% CI 0.60, 0.63) in validation. Using derivation cut-offs, KidneyIntelX stratified 46%, 37% and 17% of the validation cohort into low-, intermediate- and high-risk groups for the composite kidney endpoint, respectively. The PPV for progressive decline in kidney function in the high-risk group was 61% for KidneyIntelX vs 40% for the highest risk strata by KDIGO categorisation (p < 0.001). Only 10% of those scored as low risk by KidneyIntelX experienced progression (i.e., NPV of 90%). The NRIevent for the high-risk group was 41% (p < 0.05). CONCLUSIONS: KidneyIntelX improved prediction of kidney outcomes over KDIGO and clinical models in individuals with early stages of DKD.

Fibrinogen Early In Severe Trauma studY (FEISTY): results from an Australian multicentre randomised controlled pilot trial.

Background: Haemorrhage is a major cause of death in severe trauma. Fibrinogen plays a critical role in maintaining haemostasis in traumatic haemorrhage, and early replacement using fibrinogen concentrate (FC) or cryoprecipitate (Cryo) is recommended by several international trauma guidelines. Limited evidence supports one product over the other, with widespread geographic and institutional variation in practice. Two previous trials have investigated the feasibility of rapid FC administration in severely injured trauma patients, with conflicting results. Objective: To compare the time to fibrinogen replacement using FC or Cryo in severely injured trauma patients with major haemorrhage and hypofibrinogenaemia. Design, setting, patients and interventions: A multicentre controlled pilot trial in which adult trauma patients with haemorrhage were randomly assigned (1:1) to receive FC or Cryo for fibrinogen replacement, guided by FIBTEM A5 (functional fibrinogen assessment at 5 minutes after clot formation, using rotational thromboelastometry). Main outcome measures: The primary outcome was time to commencement of fibrinogen replacement. Secondary outcomes included effects of the intervention on plasma fibrinogen levels and clinical outcomes including transfusion requirements and mortality. Results: Of the 100 randomly assigned patients, 62 were hypofibrinogenaemic and received the intervention (n = 37) or Cryo (n = 25). Median (interquartile range [IQR]) time to delivery of FC was 29 min (23-40 min) compared with 60 min (40-80 min) for Cryo (P = 0.0001). All 62 patients were hypofibrinogenaemic before receiving FC or Cryo (FC: median FIBTEM A5, 8 mm [IQR, 7-9 mm]; Cryo: median FIBTEM A5, 9 mm [IQR, 5-10 mm]). In the FC arm patients received a median of 3 g FC (IQR, 2-4 g), and in the Cryo arm patients received a median of 8 units of Cryo (IQR, 8-14 units). Restoration of fibrinogen levels was achieved in both arms after the intervention. Blood product transfusion, fluid resuscitation and thromboembolic complications were similar in both arms. Overall mortality was 15.3%, with more deaths in the FC arm. Conclusion: Fibrinogen replacement in severely injured trauma patients with major haemorrhage and hypofibrinogenaemia was achieved substantially faster using FC compared with Cryo. Fibrinogen levels increased appropriately using either product. The optimal method for replacing fibrinogen in traumatic haemorrhage is controversial. Our results will inform the design of a larger trial powered to assess patient-centred outcomes.

Targeted cryoprecipitate transfusion in severe traumatic haemorrhage.

BACKGROUND: Severe traumatic haemorrhage is the leading cause of death in young adults. Trauma Induced Coagulopathy is a complex and multifactorial phenomenon associated with severe traumatic haemorrhage. Fibrinogen is one of the first coagulation factors to become depleted in TIC and evidence suggests that severely injured trauma patients with hypofibrinogenaemia have poor outcomes. It is postulated that early fibrinogen replacement can improve clinical outcomes. This study investigated cryoprecipitate transfusion in hyopfibrinogeneamic trauma patients. METHODS: This retrospective, single center, observational study investigated the use of cryoprecipitate in severely injured trauma patients admitted to an Australian Level I Trauma Centre. The primary outcome was time to administration of cryoprecipitate after identification of hypofibrinogenaemia using ROTEM (FIBTEM A5). Data collected included demographics, ISS, laboratory values of coagulation and blood product usage. RESULTS: 71 patients received cryoprecipitate with a median time of 61 minutes [IQR 37-93] from FIBTEM A5 result to initial cryoprecipitate administration. At 24 hours following admission to ED, Clauss Fibrinogen levels increased by 1.30g/L [IQR 0.45-1.85] and FIBTEM A5 assay increased by 8mm [IQR 3.0-11.3]. Changes in both variables were highly significant (p<0.001) and Clauss Fibrinogen versus FIBTEM A5 values showed moderate to strong correlation (R=0.75-0.80). CONCLUSION: This study demonstrated that early administration of cryoprecipitate was both feasible and efficacious in fibrinogen replacement in severe traumatic haemorrhage. High-level evidence supporting cryoprecipitate or fibrinogen concentrate replacement with regards to efficacy and feasibility is required to guide future clinical practice. This study provided baseline data to inform the design of further clinical trials investigating fibrinogen replacement in traumatic haemorrhage.

Viscoelastic haemostatic assays in aeromedical transport.

OBJECTIVE: To assess the feasibility of using rotational thromboelastometry (ROTEM®)-sigma and thromboelastography (TEG®)-6s viscoelastic point-of-care assays during rotary wing aeromedical transport, and to determine the reliability of the results obtained. METHODS: A single centre, prospective, observational, non-interventional feasibility study performed at Gold Coast University Hospital intensive care unit, and in a LifeFlight Retrieval Medicine operated Leonardo AW139 helicopter. Blood was collected from eight healthy volunteers on 18 April 2019 and all testing was performed on that day. Functions measured were ROTEM-sigma extrinsically activated thromboelastometry (EXTEM) clotting time (CT), EXTEM amplitude at 5 min after CT (A5) and fibrin-based extrinsically activated thromboelastometry (FIBTEM) A5, and TEG-6s Kaolin (CK) reaction time (R), functional fibrinogen (CFF) maximal amplitude (MA) and CFF amplitude at 10 min after R (A10). Differences between the results obtained in the helicopter and control results at Gold Coast University Hospital during flight and after flight, and also differences in control results over time up to 3 h were analysed. RESULTS: During flight both the ROTEM-sigma and TEG-6s devices failed to give reliable results. Post flight, the helicopter and control samples correlated well. Repeat testing of control samples at 1 and 3 h also revealed good correlation over time. CONCLUSION: It is feasible to reliably run tests on both the ROTEM-sigma and TEG-6s after the devices have been flown in a rotary wing aircraft. However, testing cannot be performed while in flight conditions. It is also possible to run blood samples collected up to 3 h prior and acquire results which correlate well with initial testing.

Initial Validation of a Machine Learning-Derived Prognostic Test (KidneyIntelX) Integrating Biomarkers and Electronic Health Record Data To Predict Longitudinal Kidney Outcomes.

Background: Individuals with type 2 diabetes (T2D) or the apolipoprotein L1 high-risk (APOL1-HR) genotypes are at increased risk of rapid kidney function decline (RKFD) and kidney failure. We hypothesized that a prognostic test using machine learning integrating blood biomarkers and longitudinal electronic health record (EHR) data would improve risk stratification. Methods: We selected two cohorts from the Mount Sinai BioMe Biobank: T2D (n=871) and African ancestry with APOL1-HR (n=498). We measured plasma tumor necrosis factor receptors (TNFR) 1 and 2 and kidney injury molecule-1 (KIM-1) and used random forest algorithms to integrate biomarker and EHR data to generate a risk score for a composite outcome: RKFD (eGFR decline of ≥5 ml/min per year), or 40% sustained eGFR decline, or kidney failure. We compared performance to a validated clinical model and applied thresholds to assess the utility of the prognostic test (KidneyIntelX) to accurately stratify patients into risk categories. Results: Overall, 23% of those with T2D and 18% of those with APOL1-HR experienced the composite kidney end point over a median follow-up of 4.6 and 5.9 years, respectively. The area under the receiver operator characteristic curve (AUC) of KidneyIntelX was 0.77 (95% CI, 0.75 to 0.79) in T2D, and 0.80 (95% CI, 0.77 to 0.83) in APOL1-HR, outperforming the clinical models (AUC, 0.66 [95% CI, 0.65 to 0.67] and 0.72 [95% CI, 0.71 to 0.73], respectively; P<0.001). The positive predictive values for KidneyIntelX were 62% and 62% versus 46% and 39% for the clinical models (P<0.01) in high-risk (top 15%) stratum for T2D and APOL1-HR, respectively. The negative predictive values for KidneyIntelX were 92% in T2D and 96% for APOL1-HR versus 85% and 93% for the clinical model, respectively (P=0.76 and 0.93, respectively), in low-risk stratum (bottom 50%). Conclusions: In patients with T2D or APOL1-HR, a prognostic test (KidneyIntelX) integrating biomarker levels with longitudinal EHR data significantly improved prediction of a composite kidney end point of RKFD, 40% decline in eGFR, or kidney failure over validated clinical models.

Characteristics of the Optimal Cognitive Behavioral Analysis System of Psychotherapy (CBASP) Therapist Role.

The characteristics of the optimal CBASP therapist role for the treatment of the Persistent Depressive Disorder patient (chronic depression) is delineated in this paper. This paper contains the opinions and experiences of the creator of CBASP who has developed and revised the model over more than 4 decades. The paper is not a rigorous study nor a review of rigorous studies. The difficulties of the patient are briefly discussed and then the characteristics of the optimal clinical role are presented. The clinical role of CBASP, the only model to have been developed specifically to treat the chronically depressive patient, is unique in the field of psychotherapy. Four role categories describing the behavior of the best therapists are presented and discussed: (1) the therapist is able to enact a Disciplined Personal Involvement clinical role with the patient; (2) the therapist is able to implement an acquisition-learning approach to therapeutic administration; (3) the practitioner is able to adhere to the standards of CBASP technique administration; and finally, (4) the clinician is able to implement several facilitative interpersonal skills.

Do interpersonal fears mediate the association between childhood maltreatment and interpersonal skills deficits? A matched cross-sectional analysis.

Objective: Childhood maltreatment, interpersonal fear and a specific kind of interpersonal skills deficit (preoperational thinking) have all been associated with persistent depressive disorder (PDD). We hypothesize that interpersonal fears mediate the association between childhood maltreatment and preoperational thinking.Method: A total of 108 matched participants have been examined cross-sectionally (31 healthy controls, 30 patients with episodic depression and 47 patients with PDD) with the following instruments: the Childhood Trauma Questionnaire (CTQ-SF), a measure of interpersonal fear (CBASP Interpersonal Questionnaire) and the Lübeck Questionnaire of Preoperational Thinking.Results: Patients with PDD reported significantly more childhood maltreatment than patients with episodic depression (d = 0.65) and healthy controls (d = 1.29). They also had more interpersonal fears (d = 0.71 and d = 2.11 respectively) and higher levels of preoperational thinking (d = 0.90 and d = 2.78 respectively). The association between childhood maltreatment and preoperational thinking was mediated through interpersonal fears.Conclusions: Our findings might have important implications for psychotherapy of PDD because they demonstrate how specific problems in social interactions can be associated with interpersonal fears that arise secondary to childhood maltreatment.

The Statistical Curriculum Within Randomized Controlled Trials in Critical Illness.

OBJECTIVES: Incomplete biostatistical knowledge among clinicians is widely described. This study aimed to categorize and summarize the statistical methodology within recent critical care randomized controlled trials. DESIGN: Descriptive analysis, with comparison of findings to previous work. SETTING: Ten high-impact clinical journals publishing trials in critical illness. SUBJECTS: Randomized controlled trials published between 2011 and 2015 inclusive. INTERVENTIONS: Data extraction from published reports. MEASUREMENTS AND MAIN RESULTS: The frequency and overall proportion of each statistical method encountered, grouped according to those used to generate each trial's primary outcome and separately according to underlying statistical methodology. Subsequent analysis compared these proportions with previously published reports. A total of 580 statistical tests or methods were identified within 116 original randomized controlled trials published between 2011 and 2015. Overall, the chi-square test was the most commonly encountered (70/116; 60%), followed by the Cox proportional hazards model (63/116; 54%) and logistic regression (53/116; 46%). When classified according to underlying statistical assumptions, the most common types of analyses were tests of 2 × 2 contingency tables and nonparametric tests of rank order. A greater proportion of more complex methodology was observed compared with trial reports from previous work. CONCLUSIONS: Physicians assessing recent randomized controlled trials in critical illness encounter results derived from a substantial and potentially expanding range of biostatistical methods. In-depth training in the assumptions and limitations of these current and emerging biostatistical methods may not be practically achievable for most clinicians, making accessible specialist biostatistical support an asset to evidence-based clinical practice.

A Procedure to Graph the Quality of Psychosocial Functioning Affected by Symptom Severity.

Assessment of the variations of clinical course to aid in diagnosis, assessment of patients' functioning and to guide treatment planning has gained momentum in recent years. A specific scale is introduced to plot the temporal course to assist empirically-minded psychotherapists and researchers who treat the DSM-5 Disorders and who want to monitor the quality of the course of psychosocial functioning over time. A Timeline Course Graphing Scale to Chart the Quality of Psychosocial Functioning Affected by Symptom Severity (PFS) is described and accompanied by administration guidelines.

Introducing a Clinical Course-Graphing Scale for DSM-5 Mood Disorders.

Assessment of clinical course to aid in the diagnosis of patients and to guide treatment planning has gained momentum in recent years. A course-graphing scale for the DSM-5 Mood Disorders is presented to facilitate clinical history-taking and diagnosis of the mood disorders during the screening interview. The scale can be administered in the more traditional historytaking portion of the screening interview. The only difference is that it is a more systematic approach especially when the clinician suspects the presence of a mood disorder. The Timeline Course Graphing Scale for the DSM-5 Mood Disorders (TCGS) is described and accompanied with guidelines for administration.

A pilot study investigating the utilization of crest pads for treatment of toe callus and ulceration.

Patients with lesser-toe deformities are at increased risk of developing calluses and ulcers on the distal ends of the affected digits because of the increased pressures applied to these areas. The number of diabetic patients in the United States continues to increase, along with associated comorbidities such as peripheral vascular disease and peripheral neuropathy. These conditions predispose patients to developing foot ulcerations, especially if foot deformities are present. Crest pads are a simple-to-make, inexpensive option to treat calluses and ulcerations on the distal ends of digits; however, there is no research available that support their use. Crest pads consist of rolled gauze covered in moleskin, with a large opening that fits over several toes and lies on the dorsal aspect of the foot, with the padded portion resting under the toes. Over several days of use, the pad molds to the plantar aspect of the toes, offloading pressure from the distal end of the affected digit(s). The sample was obtained through a retrospective chart review of patients identified as having had at least one nail care visit and at least one follow-up visit at a vascular surgery practice between August 2011 and December 2014. Potential subjects with toe deformities who presented with callus or ulcer on the distal end of a digit were considered for inclusion, if they received a crest pad as part of their treatment plan. The scholarly project was a preintervention or postintervention design with subjects acting as their own controls. McNemar's test was used to analyze the results which were statistically significant (P < .0001 at first callus follow-up and P = .0002 at second callus follow-up) for callus, hemorrhagic callus, and/or ulcer improvement following the crest pad intervention. The results of this scholarly project support the use of crest pads in patients with lesser-toe deformities to treat distal toe calluses and/or ulcerations.