Tocilizumab in Severe COVID-19 Pneumonia and Concomitant Cytokine Release Syndrome

Younger patients with COVID-19 may experience an exaggerated immune response to SARS-CoV-2 infection and develop cytokine release syndrome (CRS), which may be life threatening. There is no proven antiviral therapy for COVID-19 so far, but profound immunosuppression has recently been suggested as a treatment for COVID-19-associated CRS. We present a case of life-threatening CRS caused by COVID-19 infection with a favourable response to immunosuppressive therapy with tocilizumab (TCZ). The rapid clinical and biochemical improvement following TCZ administration suggests that treatment with immunotherapy can be life-saving in selected patients with COVID-19-induced CRS

Development and Pretesting of a Questionnaire to Assess Patient Experiences and Satisfaction with Medications (PESaM Questionnaire)

Background: The aim of this study was to develop, together with the Lung Foundation Netherlands and Dutch Kidney Patients Association, patients and clinicians, a measure to evaluate patient experiences with the orphan drugs pirfenidone (for idiopathic pulmonary fibrosis [IPF]) and eculizumab (for atypical haemolytic uraemic syndrome [aHUS]), as well as a generic measure of patient experiences and satisfaction with medications. Methods: Development of the Patient Experiences and Satisfaction with Medications (PESaM) questionnaire consisted of four phases: literature review (phase I); focus groups and individual patient interviews (phase II); item generation (phase III); and face and content validity testing (phase IV). Literature review aimed to identify existing disease-specific and generic patient experience measures to provide guidance on the domains of medication use relevant to patients, the number of items and type of response categories, and to generate an initial pool of items. Subsequent focus groups and patient interviews were conducted to gain insight into the perceived effectiveness of the therapies, the bur

Validity of the Patient Experiences and Satisfaction with Medications (PESaM) Questionnaire

Background: This study assessed the validity and reliability of the generic module of the recently developed Patient Experiences and Satisfaction with Medications (PESaM) questionnaire in a sample of patients in the Netherlands. Methods: The generic module of the PESaM questionnaire consists of 18 items related to the domains effectiveness, side effects and ease of use of medications. It assesses patients’ experiences regarding the impact of the medication on daily life, health and satisfaction. In 2017, the PESaM questionnaire was sent out to idiopathic pulmonary fibrosis patients using pirfenidone or nintedanib, atypical haemolytic uraemic syndrome patients receiving eculizumab and patients using tacrolimus after kidney transplantation. Mean scores for each domain were calculated applying a scoring algorithm. Construct validity and reliability were assessed using recommended methods. Results: 188 participants completed the generic module, of whom 48% used pirfenidone, 36% nintedanib, 11% tacrolimus and 5% eculizumab. The generic module has good structural properties. Internal consistency values of the domains were satisfactory (i.e. Cronbach’s coefficient alpha above 0.7). Confirmatory factor analysis provided further evidence for construct validity, with good convergent and discriminant validity. The PESaM questionnaire also showed different scores for patients using different medications, in line with expectations, and was therefore able to differentiate between patient groups. Test–retest reliability of the items and domains were rated as moderate to fair (i.e. intraclass coefficients ranged between 0.18 and 0.76). Conclusions: The PESaM questionnaire is a unique patient-reported outcome measure evaluating patient experiences and satisfaction with medications. It has been developed in conjunction with patients, ensuring coverage of domains and issues relevant from the patient’s perspective. This study has shown promising validity of the generic module of the PESaM questionnaire. Further research is recommended to assess reliability in greater detail as well as the responsiveness of the measure. Trial registration: The study

Organ involvement and assessment in sarcoidosis

PURPOSE OF REVIEW: In recent years new recommendations have been published about organ assessment in the diagnosis of sarcoidosis. RECENT FINDINGS: Screening for pulmonary, cardiac, ocular, neurologic and renal involvement and hypercalcemia is recommended in the work-up for sarcoidosis, additionally, screening for hypercalciuria at the time of the diagnosis might be beneficial. SUMMARY: One of the goals in the work-up of sarcoidosis is to assess the extent and severity of organ involvement. Timely and accurate assessment leads to determination of treatment indication. Screening for pulmonary involvement should include pulmonary imaging and pulmonary function tests. Screening for cardiac involvement should include a clear history including palpitations and collapse and a baseline electrocardiogram or 24-h Holter monitoring. At diagnosis, ophthalmological assessment is recommended. Furthermore, serum calcium level and serum creatinine level should be obtained. Although routine 24-h urinary calcium excretion is not included in the guidelines, performing this test routinely can be considered. On indication, neurologic, rheumatologic or dermatologic assessment can be performed

Severity of pulmonary involvement and 18F-FDG PET activity in sarcoidosis

SummaryBackgroundAssessing inflammatory activity is useful in the management of persistent symptomatic sarcoidosis patients. 18F-FDG PET (PET) has been shown to be a sensitive technique to assess inflammatory activity in sarcoidosis. The aim of this study was to evaluate whether the severity of pulmonary involvement is associated with PET activity in persistent symptomatic sarcoidosis patients.MethodsOver a 5-year period, relevant clinical data including laboratory and lung function test results were gathered from the medical records of 95 sarcoidosis patients with persistent disabling symptoms who underwent both a PET and HRCT. HRCT scans were classified using a semiquantitative scoring system and PET findings as positive or negative, respectively.ResultsPET was positive in 77/95 patients, of whom 56 demonstrated pulmonary PET-positivity. HRCT scores were high (7.1 ± 3.6) in patients with positive pulmonary PET findings (n = 56) compared to patients with negative pulmonary PET findings (n = 39; 3.0 ± 2.9; p < 0.001). DLCO (65 ± 20% predicted) and FVC (85 ± 24% predicted) were low in patients with pulmonary PET-positivity versus those with negative pulmonary PET findings (79 ± 16% predicted; p = 0.001 and 96 ± 22% predicted; p = 0.044, respectively). Interestingly, out of the 26 patients with fibrotic changes, 22 (85%) had positive pulmonary PET findings, of whom 18/22 (82%) showed extrathoracic PET-positive lesions and 16/22 (73%) showed signs of serological inflammation.ConclusionsThe severity of the pulmonary involvement, assessed by HRCT features and lung function parameters, appeared to be associated with PET activity in sarcoidosis. The majority of patients with fibrotic changes demonstrated inflammatory activity at pulmonary and extrathoracic sites

Safety and tolerability of pirfenidone in asbestosis: a prospective multicenter study

Background : Pirfenidone slows down disease progression in idiopathic pulmonary fibrosis (IPF). Recent studies suggest a treatment effect in progressive pulmonary fibrosis other than IPF. However, the safety and effectiveness of pirfenidone in asbestosis patients remain unclear. In this study, we aimed to investigate the safety, tolerability and efficacy of pirfenidone in asbestosis patients with a progressive phenotype. Methods : This was a multicenter prospective study in asbestosis patients with progressive lung function decline. After a 12-week observational period, patients were treated with pirfenidone 801 mg three times a day. Symptoms and adverse events were evaluated weekly and patients completed online patient-reported outcomes measures. At baseline, start of therapy, 12 and 24 weeks, in hospital measurement of lung function and a 6 min walking test were performed. Additionally, patients performed daily home spirometry measurements. Results : In total, 10 patients were included of whom 6 patients (66.7%) experienced any adverse events during the study period. Most frequently reported adverse events were fatigue, rash, anorexia and cough, which mostly occurred intermittently and were reported as not very bothersome. No significant changes in hospital pulmonary function (forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), 6 min walking test or patient-reported outcomes measures before and after start of pirfenidone were found. Home spirometry demonstrated a FVC decline in 12 weeks before start of pirfenidone, while FVC did not decline during the 24 week treatment phase, but this difference was not statistically significant. Conclusions : Treatment with pirfenidone in asbestosis has an acceptable safety and tolerability profile and home spirometry data suggest this antifibrotic treatment might attenuate FVC decline in progressive asbestosis

Online mindfulness-based cognitive therapy for fatigue in patients with sarcoidosis (TIRED): a randomised controlled trial

Background: Sarcoidosis-associated fatigue is highly prevalent and is often reported as the most burdensome symptom of sarcoidosis. Management of fatigue is challenging, and evidence-based therapies are lacking. In this TIRED trial, we aimed to assess the effects of a 12-week online mindfulness-based cognitive therapy (eMBCT) on fatigue. Methods: This study was a prospective, open-label, multicentre randomised controlled trial, conducted at three centres in the Netherlands. Eligible patients were 18 years or older, had stable sarcoidosis, and a score of more than 21 points on the Fatigue Assessment Scale (FAS). Patients were randomised into either the eMBCT or the control group. Participants completed patient-reported outcome measures at baseline, after intervention (T1), and 12 weeks after completion of eMBCT (T2). The primary outcome was the change in FAS score at T1 in the eMBCT group compared with the control group, assessed with the independent students' t test in all patients who started the study. Secondary outcomes included within-group difference in FAS score at T1 and T2, between-group difference in FAS score at T2, and changes in the Hospital Anxiety and Depression Scale, the Freiburg Mindfulness Inventory–Short Form, and the Kings Sarcoidosis Questionnaire. The study was registered at the Netherlands Trial Register, NL7816. Findings: Between June 5, 2019, and Oct 28, 2021, 99 patients were randomly assigned to the eMBCT (n=52) or the control (n=47) groups. Six patients withdrew consent after psychological screening before the start of eMBCT. Baseline FAS score was similar in both groups (34·57 [SD 6·07] for 46 patients in the eMBCT group and 35·51 [4·65] for 47 patients in the control group). Mean change in FAS score at T1 was –4·53 (SD 5·77; p<0·0001) in the eMBCT group and –1·28 (3·80; p=0·026) in the control group (between-group difference 3·26 [95% CI 1·18 to 5·33; p=0·0025]). Furthermore, the eMBCT group had a significant improvement in anxiety (mean between-group difference 1·69, 95% CI 0·22–3·16; p=0·025), depressive symptoms (1·52, 0·08–2·95; p=0·039), mindfulness (3·1, 0·70–5·49; p=0·022), and general health status (6·28, 2·51–10·06; p=0·002) at T1, compared with the control group. Interpretation: 12 week eMBCT improves fatigue, anxiety, depression, mindfulness, and health status in patients with sarcoidosis-associated fatigue. Funding: Dutch Sarcoidosis Patient Association (Sarcoidose.nl). Translation: For the Dutch translation of the summary see Supplementary Materials section