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

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

Cricopharyngeal Myotomy in Pharyngeal Paralysis

A brief outline of the causes and symptoms of hypopharyngeal paresis is followed by a discussion of the diagnostic possibilities of manometry and cineradiography. It was found that the pharyngoesophageal sphincter mechanism remains intact in the case of complete paralysis of the hypopharynx. When there are severe symptoms of dysphagia, myotomy of the pharyngoesophageal sphincter is to be considered on the basis of these diagnostic findings. This procedure can lead to substantial improvement of the symptoms. Sphincterotomy yielded very favorable results in five out of nine patients, two of whom are discussed in some detail by way of illustration. </jats:p

The association between parent-reported and observed parenting:A multi-level meta-analysis

The purpose of the present meta-analysis was to investigate the strength of the association between parent-reported and observed parenting, and to investigate which specific characteristics of participants, questionnaires, or observational procedures moderate this association. A systematic search of relevant peer-reviewed articles published between January 2000 and December 2014 yielded 36 articles (N = 8,510) and 89 effect sizes. Results from a 3-level random-effects meta-analysis demonstrated a weak, yet significant, overall association of r = .17 between parent-reported and observed parenting. The magnitude of the effect size depended on questionnaire length (larger effect for more items) and the type of parenting investigated (largest effects for negative parent behaviors, next largest effects for positive parent behaviors, and smallest effect for controlling parent behaviors). In conclusion, this study shows that the strength of the association between parent-reported and observed parenting is small but significant

Achtergronden bij de berekening van vermesting van bodem en grondwater voor de 5e milieuverkenning met het model STONE

Ten behoeve van de vijfde milieuverkenning is de voorgenoomen Integrale Aanpak van de mestproblematiek van de Nederlandse regering doorgerekend met het model STONE. Er is gekeken naar landsdekkende milieueffecten op bodemm, bovenste grondwater en belasting van het regionale oppervlaktewater vor de periode 1986 tot 2030

Plausibiliteitsdocument STONE 2.0 (Globale verkenning van de plausibiliteit van het model STONE versie 2.0 voor de modellering van uit- en afspoeling van N en P).

STONE is ontwikkeld om landsdekkend voor Nederland de effecten van bemesting en mestbeleid op de emissies van stikstof en fosfaat uit de landbouw naar grond- en oppervlaktewater te verkennen. De nadruk in de hier gerapporteerde plausibiliteitsstudie ligt op vaststelling van de geloofwaardigheid, het realiteitsgehalte, van getalswaarden en ruimtelijke verdeling van data in STONE versie 2.0

Plausibiliteitsdocument STONE 2.0 (Globale verkenning van de plausibiliteit van het model STONE versie 2.0 voor de modellering van uit- en afspoeling van N en P).

STONE is ontwikkeld om landsdekkend voor Nederland de effecten van bemesting en mestbeleid op de emissies van stikstof en fosfaat uit de landbouw naar grond- en oppervlaktewater te verkennen. De nadruk in de hier gerapporteerde plausibiliteitsstudie ligt op vaststelling van de geloofwaardigheid, het realiteitsgehalte, van getalswaarden en ruimtelijke verdeling van data in STONE versie 2.0

Imatinib in patients with severe COVID-19: a randomised, doubleblind, placebo-controlled, clinical trial (vol 9, pg 957, 2021)

Pathogenesis and treatment of chronic pulmonary disease

Imatinib in patients with severe COVID-19: a randomised, doubleblind, placebo-controlled, clinical trial (vol 9, pg 957, 2021)

Pathogenesis and treatment of chronic pulmonary disease