12 research outputs found

    Outpatient-Based Therapy of Oral Fludarabine and Subcutaneous Alemtuzumab for Asian Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

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    Background. Intravenous alemtuzumab and fludarabine are effective in combination for the treatment of chronic lymphocytic leukemia (CLL), but require hospital visits for intravenous injection. We performed a pilot study to assess the safety and efficacy of outpatient-based oral fludarabine with subcutaneous alemtuzumab (OFSA) for the treatment of relapsed/refractory CLL. Results. Depending on their response, patients were given two to six 28-day cycles of subcutaneous alemtuzumab 30 mg on days 1,3, and 5 and oral fludarabine 40 mg/m2/day for 5 days. Median patient age was 74. The lymphocyte counts of all five patients fell after the 1st cycle of treatment and reached normal/low levels on completion of 2 to 6 cycles of therapy. Platelet counts and hemoglobin were unaffected. All five patients achieved complete hematological remission, while two attained minimal residual disease negativity on 4-color flow cytometry. Conclusions. Our OFSA regimen was effective in elderly Asian patients with relapsed/refractory CLL, and it should be investigated further

    Overview of JET results

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    High density and high confinement operation in ELMy H-mode is confirmed at or above the normalized parameters foreseen for the ITER operating point (H98(y,2) 3c 1, n/nGW 3c 1, \u3b2N > 1.8 at q95 3c 3). The scaling of the ELMy H-mode with \u3b2N could be more favourable than that predicted by the IPB98(y,2) scaling. In ELMy H-mode, ion cyclotron current drive (ICCD) control of large sawteeth stabilized by fast particle has been demonstrated and the underlying neo-classical tearing modes (NTMs) and sawtooth physics is being refined. At high-density, Type I ELMy H-modes show trends that would lead to marginally acceptable ELMs on ITER. Type II ELM regime has been produced, though under very restrictive conditions. Type III ELMy operation with radiation fractions up to 95% has been demonstrated by seeding of N2 in H-modes and could extrapolate to Q = 10 ITER operation, albeit at high current (17 MA). The mitigation of Type I ELMs, nevertheless, remains a challenge. Considerable progress has been obtained in internal transport barrier (ITB) plasmas, with operation at central densities close to the Greenwald density or/and low toroidal rotation or/and high triangularity. Demonstrations of full current drive and successful simultaneous real time control of safety factor and temperature profiles have been achieved in ITB plasmas. Physics of resistive wall modes (RWMs) has been compared with theory, showing favourable scaling for ITER. High \u3b2N 3c 2.8 operation of hybrid modes (also called improved H-modes) has been obtained with dominant neutral beam heating. Hybrid modes with dominant ion cyclotron resonance heating (ICRH) have also been achieved. Trace tritium experiments yielded valuable information on particle transport in H-mode, ITB and hybrid regimes. In Type I ELMy plasmas, successful tests of the conjugate-T ICRH scheme have been achieved as well as lower hybrid coupling at ITER-relevant 10\u201311 cm distances. Reduced D and T fuel retention has been observed, which could relate to operation with vertical targets in the divertor and/or lower (ITER-like) vessel temperature. It is confirmed that erosion occurs predominantly on the main chamber surfaces, with possible benefits for T retention in ITER, although consequences for the metallic first wall lifetime need to be assessed. Disruption and ELM studies indicate that transient power deposition could be less constraining than expected for the ITER divertor, but more challenging for the metallic first wall. Alpha particle tomography and direct observation of alpha particle slowing down have been made possible by \u3b3 -spectroscopy. Measurements of Alfve \u301n cascades have been improved by a new interferometric technique. Promising tests of ITER relevant neutron counting detectors have been conducted

    Empowering People to Choose Wisely via Mindfulness and Thinking Tools

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    Microwave ferrites, part 1: fundamental properties

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    Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

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    Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities

    Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19

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    Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes

    Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry

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    Background: COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs). Objectives: The main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality. Methods: Adult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions. Results: The study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51). Conclusion: In a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings

    The value of open-source clinical science in pandemic response: lessons from ISARIC

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    The value of open-source clinical science in pandemic response: lessons from ISARIC

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