ObjectiveRecent clinical studies have shown that anticoagulant therapy might be effective only in specific at-risk subgroups of patients with sepsis and coagulation dysfunction. The definition of ...sepsis was recently modified, and as such, old scoring systems may no longer be appropriate for the diagnosis of sepsis-associated coagulopathy. The aim of this study was to evaluate prognostic factors in patients diagnosed with sepsis and coagulopathy according to the new sepsis definition and assess their accuracy in comparison with existing models.DesignRetrospective analysis of the nationwide survey for recombinant human soluble thrombomodulin.SettingGeneral emergency and critical care centres in secondary and tertiary care hospitals.ParticipantsWe evaluated the prognostic value of the newly proposed diagnostic criteria for sepsis-induced coagulopathy (SIC). A total of 1498 Japanese patients with sepsis and coagulopathy complications who were treated with recombinant thrombomodulin were analysed in this study.Main outcome measuresThe platelet count, prothrombin time (PT) ratio, fibrinogen/fibrin degradation products, systemic inflammatory response syndrome score and Sequential Organ Failure Assessment (SOFA) score obtained just before the start of treatment were examined in relation to the 28-day mortality rate.ResultsThe platelet count, PT ratio and total SOFA were independent predictors of a fatal outcome in a logistic regression model. A SIC score was defined using the three above-mentioned variables with a positivity threshold of 4 points or more. The SIC score predicted higher 28-day mortality rate compared with the current Japanese Association for Acute Medicine-disseminated intravascular coagulation score (38.4%vs34.7%).ConclusionThe SIC score is based on readily available parameters, is easy to calculate and has a high predictive value for 28-day mortality. Future studies are warranted to evaluate whether the SIC score may guide the decision to initiate anticoagulant therapy.
Deep vein thrombosis and pulmonary embolism Di Nisio, Marcello, Dr; van Es, Nick, MD; Büller, Harry R, MD
The Lancet (British edition),
12/2016, Letnik:
388, Številka:
10063
Journal Article
Recenzirano
Summary Deep vein thrombosis and pulmonary embolism, collectively referred to as venous thromboembolism, constitute a major global burden of disease. The diagnostic work-up of suspected deep vein ...thrombosis or pulmonary embolism includes the sequential application of a clinical decision rule and D-dimer testing. Imaging and anticoagulation can be safely withheld in patients who are unlikely to have venous thromboembolism and have a normal D-dimer. All other patients should undergo ultrasonography in case of suspected deep vein thrombosis and CT in case of suspected pulmonary embolism. Direct oral anticoagulants are first-line treatment options for venous thromboembolism because they are associated with a lower risk of bleeding than vitamin K antagonists and are easier to use. Use of thrombolysis should be limited to pulmonary embolism associated with haemodynamic instability. Anticoagulant treatment should be continued for at least 3 months to prevent early recurrences. When venous thromboembolism is unprovoked or secondary to persistent risk factors, extended treatment beyond this period should be considered when the risk of recurrence outweighs the risk of major bleeding.
Venous thromboembolism (VTE) is a common complication among patients with cancer. Patients with cancer and VTE are at a markedly increased risk for morbidity and mortality.
These evidence-based ...guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about the prevention and treatment of VTE in patients with cancer.
ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The guideline development process was supported by updated or new systematic evidence reviews. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess evidence and make recommendations.
Recommendations address mechanical and pharmacological prophylaxis in hospitalized medical patients with cancer, those undergoing a surgical procedure, and ambulatory patients receiving cancer chemotherapy. The recommendations also address the use of anticoagulation for the initial, short-term, and long-term treatment of VTE in patients with cancer.
Strong recommendations include not using thromboprophylaxis in ambulatory patients receiving cancer chemotherapy at low risk of VTE and to use low-molecular-weight heparin (LMWH) for initial treatment of VTE in patients with cancer. Conditional recommendations include using thromboprophylaxis in hospitalized medical patients with cancer, LMWH or fondaparinux for surgical patients with cancer, LMWH or direct oral anticoagulants (DOAC) in ambulatory patients with cancer receiving systemic therapy at high risk of VTE and LMWH or DOAC for initial treatment of VTE, DOAC for the short-term treatment of VTE, and LMWH or DOAC for the long-term treatment of VTE in patients with cancer.
Background
The number of people living with dementia is increasing rapidly. Clinical dementia does not develop suddenly, but rather is preceded by a period of cognitive decline beyond normal ...age‐related change. People at this intermediate stage between normal cognitive function and clinical dementia are often described as having mild cognitive impairment (MCI). Considerable research and clinical efforts have been directed toward finding disease‐modifying interventions that may prevent or delay progression from MCI to clinical dementia.
Objectives
To evaluate the effects of at least 12 weeks of computerised cognitive training (CCT) on maintaining or improving cognitive function and preventing dementia in people with mild cognitive impairment.
Search methods
We searched to 31 May 2018 in ALOIS (www.medicine.ox.ac.uk/alois) and ran additional searches in MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO portal/ICTRP (www.apps.who.int/trialsearch) to identify published, unpublished, and ongoing trials.
Selection criteria
We included randomised controlled trials (RCTs) and quasi‐RCTs in which cognitive training via interactive computerised technology was compared with an active or inactive control intervention. Experimental computerised cognitive training (CCT) interventions had to adhere to the following criteria: minimum intervention duration of 12 weeks; any form of interactive computerised cognitive training, including computer exercises, computer games, mobile devices, gaming console, and virtual reality. Participants were adults with a diagnosis of mild cognitive impairment (MCI) or mild neurocognitive disorder (MND), or otherwise at high risk of cognitive decline.
Data collection and analysis
Two review authors independently extracted data and assessed risk of bias of the included RCTs. We expressed treatment effects as mean differences (MDs) or standardised mean differences (SMDs) for continuous outcomes and as risk ratios (RRs) for dichotomous outcomes. We used the GRADE approach to describe the overall quality of evidence for each outcome.
Main results
Eight RCTs with a total of 660 participants met review inclusion criteria. Duration of the included trials varied from 12 weeks to 18 months. Only one trial used an inactive control. Most studies were at unclear or high risk of bias in several domains. Overall, our ability to draw conclusions was hampered by very low‐quality evidence. Almost all results were very imprecise; there were also problems related to risk of bias, inconsistency between trials, and indirectness of the evidence.
No trial provided data on incident dementia. For comparisons of CCT with both active and inactive controls, the quality of evidence on our other primary outcome of global cognitive function immediately after the intervention period was very low. Therefore, we were unable to draw any conclusions about this outcome.
Due to very low quality of evidence, we were also unable to determine whether there was any effect of CCT compared to active control on our secondary outcomes of episodic memory, working memory, executive function, depression, functional performance, and mortality. We found low‐quality evidence suggesting that there is probably no effect on speed of processing (SMD 0.20, 95% confidence interval (CI) ‐0.16 to 0.56; 2 studies; 119 participants), verbal fluency (SMD ‐0.16, 95% CI ‐0.76 to 0.44; 3 studies; 150 participants), or quality of life (mean difference (MD) 0.40, 95% CI ‐1.85 to 2.65; 1 study; 19 participants).
When CCT was compared with inactive control, we obtained data on five secondary outcomes, including episodic memory, executive function, verbal fluency, depression, and functional performance. We found very low‐quality evidence; therefore, we were unable to draw any conclusions about these outcomes.
Authors' conclusions
Currently available evidence does not allow us to determine whether or not computerised cognitive training will prevent clinical dementia or improve or maintain cognitive function in those who already have evidence of cognitive impairment. Small numbers of trials, small samples, risk of bias, inconsistency between trials, and highly imprecise results mean that it is not possible to derive any implications for clinical practice, despite some observed large effect sizes from individual studies. Direct adverse events are unlikely to occur, although the time and sometimes the money involved in computerised cognitive training programmes may represent significant burdens. Further research is necessary and should concentrate on improving methodological rigour, selecting suitable outcomes measures, and assessing generalisability and persistence of any effects. Trials with long‐term follow‐up are needed to determine the potential of this intervention to reduce the risk of dementia.
Correspondence to Dr Giustino Parruti, Infectious Diseases Unit, Pescara Hospital, Pescara 65124, Italy; parrutig@gmail.com Many patients with severe COVID-19 rapidly progress to critical disease ...with refractory hypoxemia requiring invasive mechanical ventilation (IMV).1 Elevated levels of C reactive protein (CRP) and interleukin-6 (IL-6), reflecting an hyperinflammatory response, identify patients at risk of progression to refractory hypoxemia and death.2 Recent evidences suggested that high-dose intravenous tocilizumab (TCZ), a humanised anti-IL-6 receptor antibody, may rapidly reduce fever and inflammatory markers, and improve oxygenation in severe to critical COVID-19.3–5 Data on the safety and efficacy of subcutaneous TCZ, already approved for the treatment of rheumatoid arthritis, are limited. In this retrospective case–control study, we treated with TCZ 324 mg, given as two concomitant subcutaneous injections, all consecutive patients at Pescara General Hospital, Italy between 28 March and 21 April 2020, with laboratory-confirmed COVID-19 pneumonia (involving ≥20% of lung parenchyma on chest CT), hyperinflammation (CRP ≥20 mg/dL), hypoxemia (oxygen saturation <90% on room air) requiring supplemental oxygen through nasal cannulas or mask, who had no contraindications to treatment such as bacterial or fungal infection, neutropenia or liver injury. None of the patients experienced neutropenia (absolute neutrophil count <1000/mm3), one (2.5%) developed bacterial pneumonia while on IMV, as compared with three (7.5%) in the SOC group, and one (2.5%) had transient moderate liver injury (elevation in alanine aminotransferase five times above the upper limit of normal value), as compared with none in the SOC group (online supplementary table 2).
The cornerstone of the management of disseminated intravascular coagulation (DIC) is the treatment of the underlying condition triggering the coagulopathy. However, a number of uncertainties remain ...over the optimal supportive treatment. The aim of this study was to provide evidence and expert-based recommendations on the optimal supportive haemostatic and antithrombotic treatment strategies for patients with DIC. A working group defined five relevant clinical scenarios. Published studies were systematically searched in the MEDLINE and EMBASE databases (up to May 2014). Seven internationally recognised experts were asked to independently provide clinical advice. A two-phase blinded data collection technique was used to reach consensus. Only three randomised controlled trials (RCTs) on the supportive management of DIC were identified. The RCTs (overall less than 100 patients) investigated the use of fresh frozen plasma and platelet transfusion and found no differences in survival between the intervention and control groups. The experts' approach was heterogeneous, although there was consensus that supportive management should vary according to the underlying cause, clinical manifestations and severity of blood test abnormalities. Platelet transfusion should be given to maintain platelet count > 50×10⁹/l in case of bleeding while a lower threshold of 20 to 30×10⁹/l may be used in DIC without bleeding. Thromboprophylaxis with low-molecular-weight heparin is advised until bleeding ensues or platelet count drops below 30×10⁹/l. In conclusion, in the absence of solid evidence from RCTs, an individualised supportive management of DIC is advisable based on the type of underlying disease, presence of bleeding or thrombotic complications and laboratory tests results.
The incidence of acute complications and mortality associated with COVID-19 remains poorly characterized. The aims of this systematic review and meta-analysis were to summarize the evidence on ...clinically relevant outcomes in hospitalized patients with COVID-19.
MEDLINE, EMBASE, PubMed, and medRxiv were searched up to April 20, 2020, for studies including hospitalized symptomatic adult patients with laboratory-confirmed COVID-19. The primary outcomes were all-cause mortality and acute respiratory distress syndrome (ARDS). The secondary outcomes included acute cardiac or kidney injury, shock, coagulopathy, and venous thromboembolism. The main analysis was based on data from peer-reviewed studies. Summary estimates and the corresponding 95% prediction intervals (PIs) were obtained through meta-analyses.
A total of 44 peer-reviewed studies with 14,866 COVID-19 patients were included. In general, risk of bias was high. All-cause mortality was 10% overall (95% PI, 2 to 39%; 1687/14203 patients; 43 studies), 34% in patients admitted to intensive care units (95% PI, 8 to 76%; 659/2368 patients; 10 studies), 83% in patients requiring invasive ventilation (95% PI, 1 to 100%; 180/220 patients; 6 studies), and 75% in patients who developed ARDS (95% PI, 35 to 94%; 339/455 patients; 11 studies). On average, ARDS occurred in 14% of patients (95% PI, 2 to 59%; 999/6322 patients; 23 studies), acute cardiac injury in 15% (95% PI, 5 to 38%; 452/2389 patients; 10 studies), venous thromboembolism in 15% (95% PI, 0 to 100%; patients; 3 studies), acute kidney injury in 6% (95% PI, 1 to 41%; 318/4682 patients; 15 studies), coagulopathy in 6% (95% PI, 1 to 39%; 223/3370 patients; 9 studies), and shock in 3% (95% PI, 0 to 61%; 203/4309 patients; 13 studies).
Mortality was very high in critically ill patients based on very low-quality evidence due to striking heterogeneity and risk of bias. The incidence of clinically relevant outcomes was substantial, although reported by only one third of the studies suggesting considerable underreporting.
PROSPERO registration ID for this study is CRD42020177243 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=177243 ).
In a randomized trial, 1050 patients with cancer who had acute venous thromboembolism were assigned to receive either dalteparin or edoxaban for 6 to 12 months. Edoxaban was noninferior to dalteparin ...with respect to the outcome of recurrent venous thromboembolism or major bleeding.
Splanchnic vein thrombosis (SVT) including portal, mesenteric, splenic vein thrombosis and the Budd-Chiari syndrome, is a manifestation of unusual site venous thromboembolism. SVT presents with a ...lower incidence than deep vein thrombosis of the lower limbs and pulmonary embolism, with portal vein thrombosis and Budd-Chiari syndrome being respectively the most and the least common presentations of SVT. SVT is classified as provoked if secondary to a local or systemic risk factor, or unprovoked if the causative trigger cannot be identified. Diagnostic evaluation is often affected by the lack of specificity of clinical manifestations: the presence of one or more risk factors in a patient with a high clinical suspicion may suggest the execution of diagnostic tests. Doppler ultrasonography represents the first line diagnostic tool because of its accuracy and wide availability. Further investigations, such as computed tomography and magnetic resonance angiography, should be executed in case of suspected thrombosis of the mesenteric veins, suspicion of SVT-related complications, or to complete information after Doppler ultrasonography. Once SVT diagnosis is established, a careful patient evaluation should be performed in order to assess the risks and benefits of the anticoagulant therapy and to drive the optimal treatment intensity. Due to the low quality and large heterogeneity of published data, guidance documents and expert opinion could direct therapeutic decision, suggesting which patients to treat, which anticoagulant to use and the duration of treatment.
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