Suboptimal plasma concentrations with posaconazole suspension as prophylaxis in critically ill COVID-19 patients at risk of Covid-associated pulmonary aspergillosis.

WHAT IS KNOWN AND OBJECTIVE: The safety and efficacy of different antifungal agents in the prophylaxis of invasive fungal infection in patients with haematological disorders are known. We comment on the poor bioavailability of posaconazole suspension to suggest that it is not useful in critically ill COVID patients. COMMENT: The increased mortality and high incidence of COVID-associated pulmonary aspergillosis (CAPA) might justify administration of off-label posaconazole for preventing CAPA, being the only drug officially registered for prophylaxis of fungal infections. We decided to initiate off-label posaconazole prophylaxis in COVID-19 patients, who were mechanically ventilated and exposed to high-dose steroids for progressive pulmonary disease or ARDS. We found that posaconazole suspension was inadequate. Very low trough levels were observed after administration, and the dose adjustments necessary for the therapeutic drug monitoring (TDM) of the drug in our critically ill ICU patients were not useful. WHAT IS NEW AND CONCLUSION: Posaconazole suspension should not be used to prevent CAPA in COVID-19 patients on high-dose steroid therapy.

Does immediate smart feedback on therapy adherence and inhalation technique improve asthma control in children with uncontrolled asthma? A study protocol of the IMAGINE I study.

BACKGROUND: Many asthmatic children suffer from uncontrolled asthma with frequent exacerbations, despite an optimal treatment plan using inhalation medication. Studies have shown that therapy adherence and inhalation technique are often suboptimal in asthmatic children, but these have traditionally been hard to measure. A novel device functioning as an add-on to the inhaler has been developed to measure both aspects by recording vibration patterns during inhalation. This data can be converted to smart feedback and provided to patients immediately via a mobile application. The aim of this study is to improve asthma control in children between 6 and 18 years old by providing immediate smart feedback on the intake of inhalation medication. Asthma control will be measured by forced expiratory volume in 1 s, (Childhood) Asthma Control Test ((c-)ACT) score, and lung function variability and reversibility. METHODS: The study will be performed in Medisch Spectrum Twente (Enschede, The Netherlands). The goal is to include 68 uncontrolled moderate to severe asthmatic children between 6 and 18 years old who receive controller inhalation medication through the Nexthaler®, Ellipta®, or Spiromax®. The study consists of three phases. Phase 1 is observational and will last 4 weeks to observe the baseline adherence and inhalation technique as monitored by the add-on device. A randomised controlled trial lasting 6 weeks will be performed in phase 2. Patients in the intervention group will receive immediate smart feedback about the performed inhalations via a mobile application. In the control group, adherence and inhalation technique will be monitored, but patients will not receive feedback. In phase 3, also lasting 6 weeks, the feedback will be ceased for all children and revision of current therapy may occur, depending on the findings in phase 2. Asthma control can be assessed by means of spirometry (both at home and in the hospital) and (c-)ACT questionnaires. DISCUSSION: Immediate smart feedback may improve therapy adherence and inhalation technique, and thus asthma control in children and prevent unnecessary switches to targeted biologics. Performing this study in children is desired, since they are known to react differently to feedback and medication than adults. TRIAL REGISTRATION: Dutch Trial Register NL7705 . Registered on 29 April 2019.

[Agranulocytosis and septic shock after metamizole use]. / Agranulocytose en septische shock na metamizolgebruik.

BACKGROUND: Metamizole is an analgesic, the orally administered form of which was withdrawn in the Netherlands in 1989 due to an unacceptably high incidence of agranulocytosis. However, later studies showed a much lower incidence and since 2013 the use of metamizole has been recommended by the national guideline on postoperative pain. CASE DESCRIPTION: A 58-year-old woman was referred by her general practitioner to our hospital with suspected diverticulitis. Three days previously the patient had returned from a four-week period of rehabilitation at a German spa following hip replacement surgery. She had been using metamizole since the operation. Within hours of admission, the patient developed septic shock and was transferred to the intensive care unit. Laboratory tests revealed severe neutropenia of 0.2 × 10(9)/l. Treatment consisted of filgrastim, piperacillin/tazobactam and haemodynamic support. After five days the patient was sufficiently recovered to return to the ward. CONCLUSION: Metamizole-related agranulocytosis is rare but potentially life-threatening. This condition is expected to occur more frequently as the use of metamizole in the Netherlands increases.