Pharmacy compounded pilocarpine: An adequate solution to overcome shortage of pilogel® discs for sweat testing in patients with cystic fibrosis.

To respond to shortage of pilocarpine discs due to CE-licensing problems a pharmacy compounded pilocarpine HCL solution was developed and validated for use in CF diagnosis. The aim of this study was to compare the results from a pharmacy compounded pilocarpine HCL solution versus Pilogel® discs for the measurements of sweat chloride concentrations. Ten pediatric and adult patients with CF underwent a sweat test using both Pilogel® discs and pilocarpine HCL solution. The average difference between both methods was -3.25 mmol/L (95% Limits of Agreement: -7.19 [95% CI: -9.19;-5.19] and 0.69 [95% CI: -1.31;2.69] mmol/L. Passing-Bablok regression showed that zero was enclosed with the 95% CI of the calculated intercept (0.15 [95% CI: -1.70;1.42] mmol/L). These data show a good agreement in chloride concentrations obtained using the two pilocarpine products. Therefore, the pharmacy compounded pilocarpine HCL solution can be used as an alternative for Pilogel® discs during times of shortage.

The long-term safety of chronic azithromycin use in adult patients with cystic fibrosis, evaluating biomarkers for renal function, hepatic function and electrical properties of the heart.

Background: Azithromycin maintenance therapy is widely used in cystic fibrosis (CF), but little is known about its long-term safety. We investigated whether chronic azithromycin use is safe regarding renal function, hepatic cell toxicity and QTc-interval prolongation.Methods: Adult CF patients (72 patients using azithromycin for a cumulative period of 364.8 years and 19 controls, 108.8 years) from two CF-centers in the Netherlands with azithromycin (non)-use for at least three uninterrupted years were studied retrospectively.Results: There was no difference in mean decline of estimated glomerular filtration rate (eGFR), nor in occurrence of eGFR-events. No drug-induced liver injury could be attributed to azithromycin. Of the 39 azithromycin users of whom an ECG was available, 4/39 (10.3%) had borderline and 4/39 (10.3%) prolonged QTc-intervals, with 7/8 patients using other QTc-prolonging medication. Of the control patients 1/6 (16.7%) had a borderline QTc-interval, without using other QTc-prolonging medication. No cardiac arrhythmias were observed.Conclusion: We observed no renal or hepatic toxicity, nor cardiac arrythmias during azithromycin use in CF patients for a mean study duration of more than 5 years. One should be aware of possible QTc-interval prolongation, in particular in patients using other QTc-interval prolonging medication.

Colistin dry powder inhalation with the Twincer™: An effective and more patient friendly alternative to nebulization.

BACKGROUND: Nebulization of antimicrobial drugs such as tobramycin and colistin is a cornerstone in the treatment of patients with cystic fibrosis (CF) infected with Pseudomonas aeruginosa. However, nebulization has a high treatment burden. The Twincer™ is a dry powder inhaler specifically developed for the inhalation of antibiotics such as colistin. The aim of this study was to compare patient outcomes and experience with colistin dry powder by the Twincer with nebulization of colistin or tobramycin in adult CF patients in a real-life setting. METHODS: This was a retrospective study from 01-01-2015 until 01-07-2018. Effectiveness was evaluated by comparing FEV1 decline and exacerbation rate during a mean of 4.1 years of nebulization therapy prior to the initiation of the Twincer against the same values during a mean of 1.7 years of treatment with the Twincer. RESULTS: Twenty-one patients were evaluated, of whom twelve could be included in the effectiveness analysis, with a total of twenty patient years. Of all patients 71.4% preferred therapy with the Twincer over nebulization. Twincer use resulted in high treatment adherence with an average adherence rate of 92.5%. There was no significant difference in annual decline in FEV1%pred prior to and after start changing from nebulization to the use of the Twincer powder inhaler (median decline -1.56 [-5.57-5.31] and 1.35 [-8.45-6.36]) respectively, p = 0.45 (linear mixed effect model)). No significant difference was found in the number of intravenous or combined total intravenous and oral antibiotic courses during Twincer therapy compared to when using nebulization (1.68 and 2.49 courses during Twincer therapy versus 1.51 and 2.94 courses during nebulization, p = 0.88 and p = 0.63). CONCLUSION: Colistin dry powder inhalation with the Twincer is a more patient friendly alternative to nebulization, and we did not observe significant differences in the clinical outcome, regarding lung function and exacerbation rates.

Ion chromatography for the precise analysis of chloride and sodium in sweat for the diagnosis of cystic fibrosis.

BACKGROUND: Measurement of chloride in sweat is an essential part of the diagnostic algorithm for cystic fibrosis. The lack in sensitivity and reproducibility of current methods led us to develop an ion chromatography/high-performance liquid chromatography (IC/HPLC) method, suitable for the analysis of both chloride and sodium in small volumes of sweat. METHODS: Precision, linearity and limit of detection of an in-house developed IC/HPLC method were established. Method comparison between the newly developed IC/HPLC method and the traditional Chlorocounter was performed, and trueness was determined using Passing Bablok method comparison with external quality assurance material (Royal College of Pathologists of Australasia). RESULTS: Precision and linearity fulfill criteria as established by UK guidelines are comparable with inductively coupled plasma-mass spectrometry methods. Passing Bablok analysis demonstrated excellent correlation between IC/HPLC measurements and external quality assessment target values, for both chloride and sodium. With a limit of quantitation of 0.95 mmol/L, our method is suitable for the analysis of small amounts of sweat and can thus be used in combination with the Macroduct collection system. CONCLUSIONS: Although a chromatographic application results in a somewhat more expensive test compared to a Chlorocounter test, more accurate measurements are achieved. In addition, simultaneous measurements of sodium concentrations will result in better detection of false positives, less test repeating and thus faster and more accurate and effective diagnosis. The described IC/HPLC method, therefore, provides a precise, relatively cheap and easy-to-handle application for the analysis of both chloride and sodium in sweat.

[Anaphylaxis in two children caused by peanut and nut allergies; recommendations for treatment]. / Anafylaxie door pinda- en notenallergie bij 2 kinderen; aanbevelingen voor beleid.

Two girls aged 12 and 7 years with asthma and peanut and nut allergy developed anaphylactic shock after ingestion of peanuts and nuts from an unreported source. They were both given intramuscular epinephrine. The 12-year-old girl was treated clinically for shock and after two days was discharged from hospital. The 7-year-old girl died. Risk factors for life-threatening anaphylactic reactions are adolescent to young adult age, asthma, previous severe anaphylactic reactions to the food in question, previous reaction to small dose of the food in question and allergy to peanuts or tree nuts. A double-blind, placebo-controlled food challenge should be carried out to document the culprit food. The most important therapeutic intervention is the intramuscular administration of epinephrine. For patients with two or more risk factors the prescription of an epinephrine auto-injector should be considered.

[When the treatment in children with asthma fails: first other reasons should be sought before prescribing more medication]. / Wanneer de behandeling van kinderen met astma faalt: eerst op zoek naar een verklaring alvorens meer medicatie voor te schrijven.

In 4 children with asthma symptoms increased. A 13-year-old girl suffered shortness of breath from fear of a man who was making indecent advances; an 8-year-old girl was allergic to the new cat at home; a 6-year-old boy was not inhaling the medication properly; and a 6-year-old girl had tracheomalacia and a vascular ring. After the appropriate treatment policy was implemented, the symptoms reduced or the extra doses of medication were no longer needed. If the treatment of asthma in children is unsuccessful, then therapy compliance and inhalation technique should be assessed first. After that causes of failure can be excluded. Only when this has been done can the dosage of inhalation corticosteroids be increased or other medicines added to the medication therapy.

[Guideline 'Treating asthma in children' for pediatric pulmonologists (2nd revised edition). II. Medical treatment]. / Richtlijn 'Astmabehandeling bij kinderen' van kinderlongartsen (2e herziening). II. Medicamenteuze behandeling.

The second revision of the guidelines for the treatment of asthma in children is largely based on the evidence of comparative studies. Short-acting beta 2-sympathicomimetics are the medication of choice for acute exacerbations and should therefore be prescribed to each patient. Inhaled corticosteroids (ICS) are the medication of choice for maintenance treatment. Starting with a high dose of ICS which is then reduced to a lower but effective level on the basis of the complaints (step-down approach) is no longer recommended, as this strategy is not more effective than a constant dosage schedule. If asthmatic symptoms persist despite ICS maintenance treatment then 3 therapeutic options are available in the following order: doubling the ICS dose, the addition of a long-acting beta 2-sympathicomimetic, and the addition of a leukotriene receptor antagonist.

[Acute pancreatitis in children]. / Acute pancreatitis bij kinderen.

Acute pancreatitis is probably commoner in children than was previously thought. In children it is most commonly associated with trauma or viral infection. The presentation may be subtler than in adults, requiring a high index of suspicion in the clinician. In three children, two boys aged 4 and 10 and a girl of 15 years, acute pancreatitis was suspected because of the findings at ultrasonography and endoscopic retrograde cholangiopancreatography performed when the disease recurred (the boy aged 4), apathy and immobility without dehydration or other obvious causes (the boy aged 10), and severe abdominal pain in combination with vomiting (the girl). All three patients had severely increased (urinary) amylase levels. Most often, acute pancreatitis in children tends to be a self-limiting disease which responds well to conservative treatment.