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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.
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Biomarcadores/análise , Nefropatias Diabéticas/diagnóstico , Registros Eletrônicos de Saúde , Aprendizado de Máquina , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/patologia , Progressão da Doença , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Estados Unidos/epidemiologia , Adulto JovemRESUMO
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.
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Sobreviventes Adultos de Maus-Tratos Infantis , Experiências Adversas da Infância , Transtorno Depressivo/fisiopatologia , Medo/fisiologia , Trauma Psicológico/fisiopatologia , Interação Social , Habilidades Sociais , Pensamento/fisiologia , Adulto , Terapia Cognitivo-Comportamental , Estudos Transversais , Feminino , Humanos , MasculinoRESUMO
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.
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Cuidados Críticos , Interpretação Estatística de Dados , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Bibliometria , Currículo , HumanosRESUMO
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.
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Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Comportamento Social , Adulto , Progressão da Doença , Humanos , Transtornos Mentais/terapia , Guias de Prática Clínica como Assunto , Psicoterapia , Fatores de TempoRESUMO
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.
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Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Progressão da Doença , Humanos , Fatores de TempoRESUMO
BACKGROUND: Malnutrition is commonly underdiagnosed and undertreated in acute care patients. Implementation of current pathways of care is limited, potentially as a result of the perception that they are not feasible with current resources. There is a need for a pathway based on expert consensus, best practice and evidence that addresses this crisis in acute care, while still being feasible for implementation. METHODS: A modified Delphi was used to develop consensus on a new pathway. Extant literature and other resources were reviewed to develop an evidence-informed background document and draft pathway, which were considered at a stakeholder meeting of 24 experts. Two rounds of an on-line Delphi survey were completed (n = 28 and 26 participants respectively). Diverse clinicians from four hospitals participated in focus groups to face validate the draft pathway and a final stakeholder meeting confirmed format changes to make the pathway conceptually clear and easy to follow for end-users. Experts involved in this process were researchers and clinicians from dietetics, medicine and nursing, including management and frontline personnel. RESULTS: 80% of stakeholders who were invited, participated in the first Delphi survey. The two rounds of the Delphi resulted in consensus for all but two minor components of the Integrated Nutrition Pathway for Acute Care (INPAC). The format of the INPAC was revised based on the input of focus group participants, stakeholders and investigators. CONCLUSIONS: This evidence-informed, consensus based pathway for nutrition care has greater depth and breadth than prior guidelines that were commonly based on systematic reviews. As extant evidence for many best practices is absent, the modified Delphi process has allowed for consensus to be developed based on better practices. Attention to feasibility during development has created a pathway that has greater implementation potential. External validation specifically with practitioner groups promoted a conceptually easy to use format. Test site implementation and evaluation is needed to identify resource requirements and demonstrate process and patient reported outcomes resulting from embedding INPAC into clinical practice.
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Consenso , Cuidados Críticos/métodos , Desnutrição/dietoterapia , Terapia Nutricional/métodos , Adulto , Técnica Delphi , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estado NutricionalRESUMO
BACKGROUND: It is widely agreed that chronic depression is difficult to treat, knowledge about optimal treatment approaches is emerging. METHOD: A multisite randomized controlled trial was conducted comparing the cognitive behavioral analysis system of psychotherapy (CBASP), a psychotherapy model developed specifically to treat chronic depression (n = 67) with care as usual (CAU; evidence-based treatments, n = 72) over a period of 52 weeks, with 23 sessions on average, in 3 outpatient clinics in the Netherlands. In both arms algorithm-based pharmacotherapy was provided. Patients (aged 18-65) met criteria for a DSM-IV diagnosis of major depressive disorder with diagnostic specifiers (chronic, without interepisode recovery) or with co-occurring dysthymic disorder indicating a chronic course. The Inventory for Depressive Symptomatology (IDS) Self-Report was used as the primary outcome measure. Mixed-effects linear regression analysis was used to compare the changes on the IDS scores between CBASP and CAU. The IDS was administered before treatment, and after 8, 16, 32 and 52 weeks. RESULTS: At week 52, patients assigned to CBASP had a greater reduction of depressive symptoms compared to patients assigned to CAU (t = -2.00, p = 0.05). However, CBASP and CAU did not differ from each other on the IDS after 8 weeks (t = 0.49, p = 0.63), 16 weeks (t = -0.03, p = 0.98) and 32 weeks (t = -0.17, p = 0.86) of treatment. CONCLUSIONS: This trial shows that CBASP is at least as effective as standard evidence-based treatments for chronic depression. In the long run, CBASP appears to have an added effect.
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Terapia Cognitivo-Comportamental , Depressão/terapia , Adulto , Terapia Cognitivo-Comportamental/métodos , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Resultado do TratamentoRESUMO
Renal transplant recipients who experience delayed graft function have increased risks of rejection and long-term graft failure. Ischemic damage is the most common cause of delayed graft function, and although it is known that tissue inflammation accompanies renal ischemia, it is unknown whether renal ischemia affects the production of antibodies by B lymphocytes, which may lead to chronic humoral rejection and allograft failure. Here, mice immunized with a foreign antigen 24-96 hours after renal ischemia-reperfusion injury developed increased levels of antigen-specific IgG1 compared with sham-treated controls. This amplified IgG1 response did not follow unilateral ischemia, and it did not occur in response to a T-independent antigen. To test whether innate immune activation in the kidney after ischemia affects the systemic immune response to antigen, we repeated the immunization experiment using mice deficient in factor B that lack a functional alternative pathway of complement. Renal ischemia-reperfusion injury did not cause amplification of the antigen-specific antibodies in these mice, suggesting that the increased immune response requires a functional alternative pathway of complement. Taken together, these data suggest that ischemic renal injury leads to a rise in antibody production, which may be harmful to renal allografts, possibly explaining a mechanism underlying the link between delayed graft function and long-term allograft failure.
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Rejeição de Enxerto/imunologia , Imunidade Humoral/imunologia , Nefropatias/imunologia , Transplante de Rim/imunologia , Rim/imunologia , Traumatismo por Reperfusão/imunologia , Transplante Homólogo/imunologia , Animais , Nefropatias/fisiopatologia , Nefropatias/cirurgia , Camundongos , Traumatismo por Reperfusão/fisiopatologiaRESUMO
Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases.
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Micropartículas Derivadas de Células/efeitos dos fármacos , Ciclosporina/toxicidade , Células Endoteliais/efeitos dos fármacos , Imunossupressores/toxicidade , Animais , Micropartículas Derivadas de Células/metabolismo , Ativação do Complemento/efeitos dos fármacos , Complemento C3/análise , Células Endoteliais/ultraestrutura , Rim/efeitos dos fármacos , Rim/patologia , Transplante de Rim , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Tacrolimo/uso terapêuticoRESUMO
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) = 0.21ð¥ + 0.004 (where ð¥ = ROTEM® Sigma FIBTEM A5 in mm) and (g/L) = 0.16ð¥ - 0.06 (where ð¥ = 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.
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Fibrinogênio , Tromboelastografia , Ferimentos e Lesões , Humanos , Fibrinogênio/análise , Masculino , Feminino , Projetos Piloto , Adulto , Tromboelastografia/métodos , Pessoa de Meia-Idade , Austrália , Ferimentos e Lesões/sangue , Estudos Prospectivos , Testes de Coagulação Sanguínea/métodos , Testes de Coagulação Sanguínea/normas , Hemorragia/sangueRESUMO
BACKGROUND: Child maltreatment is a broadly confirmed risk factor for mental and physical illness. Some psychological treatments specifically target mental health conditions associated with child maltreatment. For example, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) focuses on maladaptive interpersonal behaviours in chronic depression. However, how the assessment of child maltreatment could inform personalised treatment is unclear. We used data from a previously published clinical trial to investigate whether a pre-established child maltreatment clustering approach predicts differential outcomes after CBASP versus non-specific supportive psychotherapy in patients with early-onset chronic depression. METHODS: We did a cluster analysis of data from a previous randomised controlled trial of unmedicated adult outpatients with early-onset chronic depression who were treated at eight university clinics and psychological institutes in Germany with 32 sessions of CBASP or non-specific supportive psychotherapy. Participants were eligible for the original trial if they were aged 18-65 years; had major depressive disorder (MDD) with an early onset and duration of at least 2 years, current MDD superimposed on a pre-existing dysthymic disorder, or recurrent MDD with incomplete remission between episodes as defined by DSM-IV; and had a score of at least 20 points on the 24-item Hamilton Rating Scale for Depression (HRSD-24). Participants were included in the current study if they had completed the short form of the Childhood Trauma Questionnaire (CTQ) at trial baseline. We used an agglomerative hierarchical clustering approach to derive child maltreatment clusters from individual patterns across the five domains of the CTQ. We used linear mixed models to investigate whether clustering could predict differential clinical outcomes (change in symptom severity on the HRSD-24) up to 2 years after treatment onset. People with lived experience were involved in the current study. FINDINGS: 253 patients (129 [51%] treated with CBASP and 124 [49%] with supportive psychotherapy) had complete CTQ records and were included in the analysis. 169 (67%) participants were women, 84 (33%) were men, and the mean age was 45·9 years (SD 11·7). We identified seven child maltreatment clusters and found significant differences in treatment effects of CBASP and supportive psychotherapy between the clusters (F(6,948·76)=2·47; p=0·023); differences were maintained over the 2-year follow-up. CBASP was superior in distinct clusters of co-occurring child maltreatment: predominant emotional neglect (change in ß -6·02 [95% CI -11·9 to -0·13]; Cohen's d=-0·98 [95% CI -1·94 to -0·02]; p=0·045), predominant emotional neglect and abuse (-6·39 [-10·22 to -2·56]; -1·04 [-1·67 to -0·42]; p=0·0011), and emotional neglect and emotional and physical abuse (-9·41 [-15·91 to -2·91]; -1·54 [-2·6 to -0·47]; p=0·0046). INTERPRETATION: CTQ-based cluster analysis can facilitate identification of patients with early-onset chronic depression who would specifically benefit from CBASP. Child maltreatment clusters could be implemented in clinical assessments and serve to develop and personalise trauma-informed care in mental health. FUNDING: The German Research Foundation and the German Federal Ministry of Education and Research.
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Terapia Cognitivo-Comportamental , Humanos , Feminino , Masculino , Adulto , Análise por Conglomerados , Terapia Cognitivo-Comportamental/métodos , Pessoa de Meia-Idade , Adulto Jovem , Resultado do Tratamento , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/psicologia , Inquéritos e Questionários , Adolescente , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Psicoterapia/métodos , Maus-Tratos Infantis/psicologia , Maus-Tratos Infantis/terapia , Criança , Testes Psicológicos , AutorrelatoRESUMO
INTRODUCTION: Hypophosphatemia is common in critically ill patients. We have described the epidemiology of hypophosphatemia in patients admitted to the Intensive Care Units. METHODS: A multicentre, retrospective cohort study of 12 ICUs in Queensland, Australia from January 1st, 2015, to December 31st, 2021. Exclusions included readmissions, renal replacement therapy, end-stage renal disease, and palliative intent admissions and transfers from other ICUs. Patients were classified into four groups based on the severity of the first episode of low serum phosphate (PO4): "None" (PO4: ≥ 0.81 mmol/L, ``Mild" (PO4: ≥ 0.50 & < 0.81 mmol/L) "Moderate" (PO4: ≥ 0.30 & < 0.50 mmol/L) and "Severe" (PO4: < 0.30 mmol/L). A mixed-effect logistic regression model, including hospital as a random effect, was developed to examine factors associated with 90-day case fatality. RESULTS: Of the 89,776 patients admitted, 68,699 patients were included in this study, with 23,485 (34.2%) having hypophosphatemia with onset mostly on Day 2 of ICU admission and correcting to normal 3 days after hypophosphatemia was identified. There was substantial variation among participating ICUs in phosphate replacement; the threshold, and the route by which it was replaced. Day-90 case fatality increased with severity of hypophosphatemia (None: 3,974 (8.8%), Mild: 2,306 (11%), Moderate: 377 (14%); Severe: 108 (21%) (p < 0.001)). Multivariable regression analysis showed that compared to those without hypophosphatemia, patients with moderate (odds ratio (OR) 1.24; 95% confidence intervals (CI) 1.07-1.44; p = 0.004) or severe (OR 1.49; 95% CI 1.13-1.97; p = 0.005) hypophosphatemia had increased risk of 90-day case fatality. CONCLUSION: Hypophosphatemia was common, and mostly occurred on day 2 with early correction of serum phosphate. Phosphate replacement practices were variable among ICUs. Moderate and severe hypophosphatemia was associated with increased 90-day case fatality.
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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.
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Oxigenação por Membrana Extracorpórea , Infecções por HIV , Masculino , Humanos , Adulto , Resultado do Tratamento , Estudos Retrospectivos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Infecções por HIV/complicações , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Sistema de Registros , HIVRESUMO
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.
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Transtornos da Coagulação Sanguínea , Tromboelastografia , Humanos , Adulto , Pessoa de Meia-Idade , Centros de Traumatologia , Estudos Retrospectivos , Austrália , QueenslandRESUMO
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.
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Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Hemostáticos , Intervenção Coronária Percutânea , Substituição da Valva Aórtica Transcateter , Humanos , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Intervenção Coronária Percutânea/métodos , Fibrinolíticos/uso terapêutico , Resultado do Tratamento , Substituição da Valva Aórtica Transcateter/métodos , Implante de Prótese de Valva Cardíaca/métodos , Heparina/uso terapêutico , Fatores de RiscoRESUMO
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.
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Injúria Renal Aguda , Sepse , Humanos , Estudos Retrospectivos , Incidência , Creatinina , Unidades de Terapia Intensiva , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Sepse/complicações , Sepse/epidemiologia , Sepse/terapiaRESUMO
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.
Assuntos
Lesões Encefálicas Traumáticas , Feminino , Humanos , Austrália , Biomarcadores , Lesões Encefálicas Traumáticas/terapia , Estudos de Coortes , Estudos Multicêntricos como Assunto , Estudos Observacionais como Assunto , Estudos ProspectivosRESUMO
The relationship between hemodynamics and thrombus deposition in abdominal aortic aneurysm is investigated for three patients (A, B and C), each with mature fusiform aneurysms. Our methodology utilises initial and follow-up computerised tomography scans for each patient to identify regions of mural thrombus growth and to provide patient-specific models for hemodynamic analysis using computational fluid dynamics. The intervals between scans for patients A, B and C were 17, 15 and 3 months, respectively. The simulations were performed using physiologically realistic boundary conditions. The hemodynamic features of the flow considered include the velocity field, the shear strain rate field, the time averaged wall shear stress and the oscillatory shear index. The parameter that showed best correlation with the location of thrombus growth was the oscillatory shear index. In particular, in the case of patient C where the interval between scans was the shortest, thrombus growth was observed at regions of low oscillatory shear index (OSI < 0.1).
Assuntos
Aorta Abdominal/fisiopatologia , Aneurisma da Aorta Abdominal/fisiopatologia , Modelos Cardiovasculares , Trombose/fisiopatologia , Idoso , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/patologia , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Simulação por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resistência ao Cisalhamento , Trombose/complicações , Trombose/patologiaRESUMO
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.