Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial

Background The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.Methods This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged >= 18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10).Findings Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0.95 [95% CI 0.76-1.20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0.51 [0.27-0.95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0.52 (95% CI 0.26-1.05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1.07 (0.63-1.80; p=0.81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0.0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events.Interpretation The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. Copyright (C) 2021 Elsevier Ltd. All rights reserved.Pathogenesis and treatment of chronic pulmonary disease

Screening and referral for psychosocial distress in oncologic practice: use of the Distress Thermometer

BACKGROUND: The objectives of this study were to validate the Distress Thermometer (DT) in the Netherlands and to examine its correspondence with a 46-item Problem List, possible risk factors, and the wish for a referral. METHODS: A cross-sectional group of 277 cancer patients who were treated at 9 hospitals filled in the DT and the Hospital Anxiety and Depression Scale and rated the presence and severity of problems (response rate, 49%). RESULTS: Receiver operating characteristic analyses identified an ideal cutoff score of 5 on the DT with a positive predictive value of 39% and a negative predictive value of 95%. The Problem List appeared to be a reliable measure. Five items on the Problem List correlated strongly with the DT, 13 items had a moderately strong correlation, 26 items were correlated weakly, and 2 items were not correlated significantly. Emotional control, nervousness, pain, and physical fitness appeared to contribute independently to the DT score. The percentage of patients scoring > or =5 (n = 118 patients; 43%) who wanted (14%) or maybe wanted (29%) a referral was significantly higher than the percentage of patients with DT scores <5 (5% and 13%, respectively) who wanted or maybe wanted a referral. Intensively treated patients reported more distress than those who only underwent surgery. No other clear risk factors for distress were identified. CONCLUSIONS: The DT appeared to be a good instrument for routine screening and ruling out elevated distress. Emotional and physical problems contributed mainly to distress. Experiencing clinically elevated distress did not necessarily suggest that patients wanted a referral. Screening for distress and the wish for a referral can facilitate providing support for those patients who most need and want it

Marital and sexual satisfaction in testicular cancer survivors and their spouses

GOAL: To compare marital and sexual satisfaction of men who survived testicular cancer (TC) and their spouses to a reference group, and to compare marital and sexual satisfaction of couples who had a relationship at time of diagnosis (couples during TC) to couples who developed a relationship after completion of treatment (couples after TC). PATIENTS AND METHODS: Two hundred and nineteen couples during TC and 40 couples after TC completed the Maudsley Marital Questionnaire, a validated instrument to measure marital and sexual satisfaction. RESULTS: Survivors and spouses of both couple groups reported similar marital satisfaction as men and women of the reference group. Survivors (t=2.9, p<0.01) and spouses (t=2.9, p<0.01) of couples during TC and survivors of couples after TC (t=1.9, p=0.05) reported less sexual satisfaction than the reference groups. Survivors of couples after TC reported less sexual satisfaction than survivors of couples during TC (F=4.0, p<0.05). Correlations between sexual satisfaction of survivors and spouses in couples during TC (r=0.76, p<0.001) and couples after TC (r=0.77, p<0.001) were high. CONCLUSION: Testicular cancer did not appear to have a negative effect on marital satisfaction in couples during TC, although TC survivors and their spouses reported less sexual satisfaction than men and women of the reference group. Survivors who developed a relationship after completion of treatment seemed to form a vulnerable group: their sexual satisfaction was lower than that of men in the reference group and of TC survivors with a longer relationship. Besides that, they more often reported marital problems than their spouses did

Quality of life and stress response symptoms in long-term and recent spouses of testicular cancer survivors

The aim of this study was to gain insight into the quality of life (QoL) and stress response of female spouses of men cured of testicular cancer in the long-term. Time since treatment completion varied from 0.5 to 23.8 years. Two hundred and fifty nine testicular cancer survivors and their spouses completed the Dutch version of the MOS Short Form (SF)-36 and the Impact of Event Scale. QoL data from a reference group of women were used for comparison. Spouses who had relationship with the testicular cancer survivor before the diagnosis (spouses during testicular cancer) had better functioning scores than the reference group, especially with respect to the physical QoL domains. Spouses who had started a relationship after treatment (spouses after testicular cancer) experienced more problems with psychological QoL domains than spouses during testicular cancer and than the reference group. The stress response of spouses during testicular cancer was related to that of the testicular cancer survivors and to the extent of treatment they had received. Although stress response levels were low, spouses during testicular cancer reported more stress response than the testicular cancer survivors. Time since completion of treatment did not affect QoL or stress response. This study showed that spouses during testicular cancer had a good QoL and little stress response. Functioning of spouses after testicular cancer was poorer with respect to various QoL domains, particularly the psychological measures

Self-esteem, social support, and mental health in survivors of testicular cancer: A comparison based on relationship status

Testicular cancer is the most frequent malignancy to men between 20 and 40 years of age. This is a period in life in which important life events take place, such as starting a career and establishing a relationship. The goal of the study was to explore self-esteem. social support. and mental health in 3 groups of survivors of testicular cancer: singles. those with the same partner as at diagnosis (relationship during testicular cancer). and those with a partner they met after completion of treatment (relationship after testicular cancer). A total of 129 survivors completed the Social Support List. the Rosenberg self-esteem scale. and the subscale mental health of the RAND-36. Mean time since diagnosis for single survivors was 8.3 years (range 1-23). for survivors with a relationship during testicular cancer 9.3 years (range 1-24), and for survivors with a relationship after testicular cancer 13.6 years (range 1-24). Levels of social support were equal ill groups. but satisfaction with support was not. Survivors with a relationship during testicular cancer were most satisfied with support, and had the highest self-esteem and mental health. Survivors with a relationship after testicular cancer reported the next best levels of functioning but had the same mental health as singles. Singles and survivors with a relationship established after testicular cancer had a lower mental health than a reference group of men. The difference in self-esteem between singles and survivors of testicular cancer with a relationship during testicular cancer appeared most distinct and was clinically relevant. Mental health was predicted by different factors for the 3 groups. Being single at diagnosis seems to cause a vulnerability that remains when survivors do develop a relationship after treatment is completed because these groups are at risk for a lower mental health. (C) 2006 Elsevier Inc. All rights reserved