The relationship between childhood leukaemia and childhood asthma: A pharmacoepidemiological study from the Netherlands.

BACKGROUND: It has been suggested that childhood asthma lowers the risk of childhood leukaemia. Studies have found an inverse association between these conditions. However, most studies on this relationship are based on questionnaires and telephone interviews, introducing recall bias. Therefore, we conducted a matched case-control study based on drug prescription data to assess the relationship between both conditions. METHODS: In a large database, covering more than one million individuals, we identified cases of children who had been prescribed 6-mercaptopurine (6-MP). This drug is used in the outpatient maintenance therapy of childhood leukaemia. We matched every child with leukaemia on sex and age (±6 months) to children without leukaemia (controls). The variable of having had asthma was defined as receiving at least two prescriptions for an inhaled corticosteroid within 12 months. RESULTS: We identified 59 children aged 2-18 who had been prescribed 6-MP (cases), and they were matched to 21,918 controls. Of the children with childhood leukaemia, three (5%) had childhood asthma, whereas in the control group 4889 (22%) had childhood asthma (odds ratio [OR] 0.19; 95% confidence interval 0.06-0.60). CONCLUSION: In this study on the relationship between childhood asthma and childhood leukaemia, we found a strong inverse association.

Conservative Treatment of Parapneumonic Effusion in Children: Experience From a 10-Year Consecutive Case Series.

BACKGROUND: In children with parapneumonic effusion (PPE), it remains unclear when conservative treatment with antibiotics suffixes or when pleural drainage is needed. In this study we evaluate clinical features and outcomes of children with PPE. METHODS: A retrospective, multicentre cohort study at 4 Dutch pediatric departments was performed, including patients 1-18 years treated for PPE between January 2010 and June 2020. RESULTS: One hundred thirty-six patients were included (mean age 8.3 years, SD 4.8). 117 patients (86%) were treated conservatively and 19 (14%) underwent pleural drainage. Patients undergoing pleural drainage had mediastinal shift more frequently compared with conservatively treated patients (58 vs. 3%, difference 55%; 95% CI: 32%-77%). The same accounted for pleural septations/pockets (58 vs. 11%, difference 47%; 95% CI: 24%-70%), pleural thickening (47 vs. 4%, difference 43%; 95% CI: 20%-66%) and effusion size (median 5.9 vs. 2.7 cm; P = 0.032). Conservative management was successful in 27% of patients (4 of 15) with mediastinal shift, 54% of patients (13 of 24) with septations/pockets, 36% of patients (5 of 14) with pleural thickening, and 9% of patients (3 of 32) with effusions >3 cm, all radiological signs generally warranting pleural drainage. In patients treated conservatively, median duration of hospitalization was 5 days (IQR 4-112) compared with 19 days (IQR 15-24) in the drainage group ( P < 0.001), without significant difference in readmission rate (11 vs. 4%, difference 6%; 95% CI: -8%-21%). CONCLUSION: This study suggests that the greater amount of children with PPE could be treated conservatively with antibiotics only, especially in absence of mediastinal shift, pleural septations/pockets, pleural thickening or extensive effusions.

[Cryptosporidiosis in a toddler]. / Cryptosporidiose bij een dreumes.

BACKGROUND: Usually, a virus is the cause of gastroenteritis in children. If the diarrhoea persists for a long time or the course is atypical, another causative agent may be the cause. CASE DESCRIPTION: We present the case history of a 15-month-old boy with atypical gastroenteritis in which he had prolonged diarrhoea and vomiting. We found a cryptosporidium as the causative agent. CONCLUSION: Especially young children, the elderly, patients with IgA deficiency or other immune disorders are at risk of severe and prolonged diarrhoea with dehydration caused by cryptosporidium. The disease is self-limiting but can sometimes become chronic. In the Netherlands no medical treatments are available. Farm animals and surface water are the main reservoirs of cryptospores. Because the sporozoites are resistant to chlorine and alcohol, elimination is difficult.

[Guideline 'Imaging with ionizing radiation': risks, communication and shielding]. / Richtlijn 'Beeldvorming met ioniserende straling'.

The guideline 'imaging with ionizing radiation' provides information about the risks when using ionizing radiation and the communication thereabout. Because most radiological investigations are performed at one time, the chance of adverse effects, is small, even in children and pregnant women. In case of complex or multiple investigations, the medical physicist can be consulted to estimate the risks. The working group recommends using population diagrams when discussing possible risks. The working group recommends giving patients/caregivers room to express their concerns and questions. The working group advices using supporting material. The working group advocates the development of nationally uniform information material. If the patient/caregiver still has concerns, the working group recommends calling in experts such as radiologists, medical physicists, and radiographers.

Low Relevancy of Outcome Measurements of Studies of Pediatric Pain in the Emergency Department.

Many children visiting the emergency department (ED) experience pain. Several pharmacological and nonpharmacological interventions are used for pain control. Little is known about the outcome measurements in studies about pain in children in the ED.Furthermore, it is not known if complete pain relief was reached. METHODS: PubMed, the Cochrane Database of Systematic Reviews, and EMBASE were searched for articles on clinical trials for pain relief in children in the ED. Inclusion criteria contained predictable and identifiable pain such as after trauma or during procedures. RESULTS: Of 620 articles found, 45 fulfilled the criteria. Twenty studies (44%) used pharmacological interventions, and 25 (56%) studied nonpharmacological interventions. In 24 studies (53%), a statistically significant pain reduction was described in the intervention group. In 21 studies (47%), a clinically relevant reduction in pain was found. In only 1 study, the reported aim was to reach absence of pain. CONCLUSION: Half of the interventions decreased pain in children in the ED. However, most studies did not aim at complete pain relief. Even in intervention groups with statistically significant decrease in pain, children still had pain. Children in the ED deserve better.Complete pain relief should be the goal of any intervention for these children in the ED.Studies on pain treatment in the ED should have complete pain relief as primary end point.

Pharmacology, particle deposition and drug administration techniques of intranasal corticosteroids for treating allergic rhinitis.

This review presents an overview of the available literature regarding intranasal corticosteroids (INCs) for the treatment of allergic rhinitis (AR). Various treatment options exist for AR including INCs, antihistamines and leucotriene antagonists. INCs are considered to be the most effective therapy for moderate-to-severe AR, as they are effective against nasal and ocular symptoms and improve quality of life. Their safety has been widely observed. INCs are effective and safe for short-term use. Local adverse events are observed but generally well-tolerated. The occurrence of (serious) systemic adverse events is unlikely but cannot be ruled out. There is a lack of long-term safety data. INC may cause serious eye complications. The risk of INCs on the hypothalamic-pituitary-adrenal axis, on bone mineral density reduction or osteoporosis and on growth in children, should be considered during treatment. Pharmacological characteristics of INCs (e.g. the mode of action and pharmacokinetics) are well known and described. We sought to gain insight into whether specific properties affect the efficacy and safety of INCs, including nasal particle deposition, which the administration technique affects. However, advances are lacking regarding the improved understanding of the effect of particle deposition on efficacy and safety and the effect of the administration technique. This review emphasizes the gaps in knowledge regarding this subject. Advances in research and health care are necessary to improve care for patients with AR.

[Damage to teeth and oral mucosa caused by inhaled drugs: you can prevent it]. / Gebitsschade door inhalatiemedicatie.

BACKGROUND: Inhaled drugs for treating asthma or chronic obstructive pulmonary disease can reduce the oral pH, impair microbial homeostasis, and induce a decrease in salivary production. These mechanisms have potential for causing damage to the teeth and oral mucosa. CASE DESCRIPTION: Until December 2021, the Netherlands Pharmacovigilance Centre Lareb received reports of 210 dental and oral mucosal adverse events while using inhaled drugs. Dental caries was most often reported. We describe three cases of tooth damage that developed within months after starting inhaled drugs. CONCLUSION: In addition to other well-known causes for tooth damage, such as neglecting oral hygiene and exposure to sugars, the use of inhaled drugs can contribute to damage to teeth. Prescribers of inhaled drugs should inform patients of the possible dental risks and prevention measures.

Adverse Drug Reactions of Intranasal Corticosteroids in the Netherlands: An Analysis from the Netherlands Pharmacovigilance Center.

BACKGROUND: Intranasal corticosteroids are one of the cornerstone treatment options for allergic rhinitis and chronic sinusitis complaints. Safety information in the summary of product characteristics may not be representative for observations in daily clinical practice. The Netherlands Pharmacovigilance Center (Lareb) collects post-marketing safety information, using spontaneous reporting systems. OBJECTIVE: Our objective was to analyse reports of adverse drug reactions associated with intranasal corticosteroids reported in the Dutch spontaneous reporting database of the Netherlands Pharmacovigilance Center Lareb to obtain insight into real-world safety data. METHODS: We retrospectively examined all adverse drug reactions of intranasal corticosteroids reported to the Netherlands Pharmacovigilance Center Lareb, entered into the database from 1991 until 1 July, 2020. RESULTS: In total, 2263 adverse drug reactions after intranasal corticosteroid use were reported in 1258 individuals. Headache (n = 143), epistaxis (n = 124) and anosmia (n = 57) were reported most frequently. Nasal septum perforation (reporting odds ratio 463.2; 95% confidence interval: 186.7-1149.7) had the highest reporting odds ratio, followed by nasal mucosal disorder (reporting odds ratio 104.5; 95% confidence interval 36.3-301.3) and hyposmia (reporting odds ratio 90.8; 95% confidence interval 45.1-182.7). Moreover, 101 (4.5%) reports were classified as serious by Lareb, including reports of Cushing's syndrome, adrenal cortical hypofunction and growth retardation. CONCLUSIONS: Many side effects are consistent with the safety information in the summary of product characteristics of intranasal corticosteroids. Several serious (systemic) side effects are reported and it is important to realise that intranasal corticosteroids may contribute to the development. Healthcare providers and patients should be aware of the potential (individual) adverse drug reactions of intranasal corticosteroids. This information could help in discussing treatment options.

[Children with atopic eczema deserve better care]. / Kinderen met eczeem verdienen betere behandeling.

Constitutional eczema in children is common. It itches and has a negative impact on quality of life. Although there are good treatments, in practice many children appear to be undertreated. Possible causes of this are: insufficient knowledge about background and treatment and insufficient cooperation between care providers. In addition, many parents are unjustly afraid of the adverse effects of hormone ointments. Some caregivers are just as afraid of hormone ointments as parents. A comment from one of them can damage the confidence of parents in the effectiveness and safety of these ointments.In our opinion, children with eczema deserve better. That is why we propose to organize regional care, education and cooperation for children with eczema. Not only general practitioners and dermatologists should participate; pharmacists and pharmacy assistants, youth health care physicians and nurses and paediatricians should also join. Information material must be uniform.

[Lifelong sequalae of adverse childhood experiences.] / De levenslange lasten van negatieve jeugdervaringen.

Negative life events in childhood can have tremendous sequalae in adulthood. Parental death in childhood is associated with reaching lower socioeconomic status, delinquency, and premature death as an adult. Exposure to four or more adverse childhood experiences, (i.e. child abuse, exposure to domestic violence, parental drug addiction, mental disorder or imprisonment) is associated with an increased risk on chronic disease in adulthood, including diabetes, mental illness, alcoholism, cancer, and cardiovascular disease. Identification of children exposed to ongoing adverse experiences is important to offer them support or help them escape. It could be helpful to ask adults if they were exposed to these experiences. If so, this could provide the possibility to offer them help when they still are hampered by these experiences. Maybe intervention could benefit them by preventing lifelong sequalae with chronic use of health care, incapacity for work, and use of medication.

Clinical characteristics of paediatric Hashimoto's encephalopathy

BACKGROUND: Hashimoto's encephalopathy, also known as steroid responsive encephalopathy, is associated with thyroid antibodies (SREAT) and is a rare but serious form of encephalopathy. In this paper, we describe the signs, symptoms, outcome, and treatments as noted in the case reports reviewed. METHODS: We searched PubMed, Embase, and the Cochrane library for articles in which cases of Hashimoto's encephalopathy were described. The case description had to include the diagnosis, age, sex, presenting symptoms, and diagnostic tests. RESULTS: We retrieved 360 articles and 65 fulfilled the inclusion criteria. These articles gave reports of 100 cases, with a mean age of 10.9 (range 2.8-19), 78 of whom were female. Epilepsy (79) - including epileptic state [24] - behavioural problems [36], hallucinations [21], headache [21], and decline in school performance [19] were most often reported. Antithyroid peroxidase (aTPO) was reported elevated in all patients. Most children [70] recovered fully, however 16 had late sequelae, mostly epilepsy. Therapies used include steroids, intravenous gammaglobulines, and cytostatics. CONCLUSIONS: Epilepsy, behavioural problems, decline in school performance, and hallucinations are frequent symptoms of Hashimoto's encephalopathy. Steroids are the basis of treatment, although other immunomodulatory drugs seem to be successful. About one in ten children will experience late sequelae. In any child with unexplained neurological, psychiatric, or psychological dysfunction, serum anti-thyroidperoxidase (aTPO) should be determined.

Reducing corticosteroid phobia in pharmacy staff and parents of children with atopic dermatitis.

Background Besides physicians, pharmacy staff has an important role to inform patients on appropriate medication use. However, they might also experience corticophobia themselves, affecting patient counseling and subsequently patient's disease management. Objective Implementation of an intervention for pharmacy staff to improve knowledge and stimulate positive perceptions towards TCS use, in order to reduce corticophobia in pharmacy staff and parents of young AD patients. Setting Nine community pharmacies in the Netherlands. Method We developed an intervention consisting of education of pharmacy staff followed by counseling of parents. The intervention was implemented in pharmacies and intervention effectiveness was studied using a pre-post design with an intervention period of 3 months. At baseline and follow-up (3 months), pharmacy staff and parents completed a questionnaire. Main outcome measure Corticophobia, both beliefs and worries, measured with the TOPICOP questionnaire. Higher scores indicate a more negative attitude. Result Baseline and follow-up data were available for 19 pharmacy staff members and 48 parents who attended a counseling session in the pharmacy. In both groups there was as decrease in negative beliefs and worries towards TCS (p < 0.05). Mean total TOPICOP scores decreased from 42 to 35% and from 33 to 25% for parents and pharmacy staff respectively. Conclusion Our results show the prevalence of corticophobia among parents. Education of pharmacy staff and targeted patient counseling seems to be effective in reducing corticophobia.

The Quality of Instructional YouTube Videos for the Administration of Intranasal Spray: Observational Study.

BACKGROUND: Allergic rhinitis is a common disorder affecting both children and adults. Recommended treatment consists of intranasal corticosteroid spray administration, but only few patients administer the nasal spray in the correct technical manner. A wrong administration technique may result in side effects and affect the efficacy and adherence, thus making accurate administration instructions indispensable. Unfortunately, information about intranasal drug administration is generally not explained accurately, thereby leading to confusion among patients and inaccuracy in the self-administration of drugs. OBJECTIVE: In this study, we analyzed instructional videos available on YouTube for the administration of nasal sprays for allergic rhinitis. Our aim was to determine if the videos provided instructions in accordance with the standardized nationwide patient protocol in the Netherlands for intranasal spray administration. METHODS: Instructional videos for the administration of aqueous formulations of nasal spray for allergic rhinitis were found on YouTube. All videos were reviewed by 2 researchers and scored using the instructions from the Dutch standardized protocol. Correct instructions were given a score of 1, while incorrect or missing instructions were given a score of 0. The interrater reliability using Cohen ĸ was used to determine the differences in the scores between the researchers. RESULTS: We identified 33 YouTube videos made by different health care professionals and pharmaceutical companies around the world. None of the videos displayed all the steps correctly, while 5 of the 33 (15%) videos displayed over 75% of the steps correctly. The median score of the correctly displayed steps was 11 out of 19 (range 2-17, IQR 6). The interrater reliability using Cohen ĸ was statistically significant (range 0.872-1.00, P<.001). The steps "neutral position of the head," "breathing out through the mouth," and "periodically cleaning with water" scored the lowest and were incorrectly displayed in 28 (85%), 28 (85%), and 30 (91%) of the 33 videos, respectively. CONCLUSIONS: The findings of our study revealed that only few instructional videos on YouTube provided correct instructions for the administration of nasal sprays to patients. The inaccuracy of the instructions for nasal spray administration in the majority of the videos may lead to confusion in patients and incorrect use of nasal sprays. In the future, it is important to make evidence-based instructional videos that show patients the correct technique of nasal spray administration. TRIAL REGISTRATION: Not applicable.

An age-adjusted instruction video enhances the correct use of nasal corticosteroid sprays in children.

INTRODUCTION AND OBJECTIVES: Allergic rhinitis is a common disorder. Intranasal corticosteroid sprays are used to control symptoms. However, incorrect use of these sprays can decrease efficacy and lead to side effects such as nose bleeding. We studied if watching an age-adjusted instruction video is effective to improve administration technique. MATERIALS AND METHODS: We invited children who used intranasal corticosteroid sprays. We examined their administration technique before, directly after, and one month after showing them an age-adjusted instruction video. We compared their administration technique with the instructions in the patient information leaflet. We assessed whether the children performed the seventeen maneuvers mentioned in the patient information leaflet and the eight we considered essential. RESULTS: Of the 99 eligible children, 23 (15 boys, median age nine years) participated. Before watching the instruction video none of them administered according to all maneuvers in the patient information leaflet or showed all essential maneuvers. One month after seeing the instruction video, three children demonstrated correct inhalation as per the patient information leaflet. Three performed the essential maneuvers. When a 75% threshold level for carrying out all 17 maneuvers was used, still none showed 75% of all or of the essential maneuvers before watching the video. Yet, after one month 12 children showed sufficient administration technique (52%, 95% confidence interval (CI) 31%-73%, p = 0.004). Nine showed all essential manoeuvres (47%, 95%CI 24%-71%, p = 0.004). CONCLUSIONS: An age-adjusted instruction video is a useful and easy method to teach children to administer nasal intranasal corticosteroid sprays correctly.

The temporal order of fluctuations in atopic disease symptoms and attention-deficit/hyperactivity disorder symptoms: a time-series study in ADHD patients.

In a recent meta-analysis, we found that atopic diseases, like asthma and allergic rhinitis, occur more frequently prior to the onset of attention-deficit/hyperactivity disorder (ADHD). Our aim was to determine the temporal order of the association between daily fluctuations in atopic disease symptoms and in ADHD symptoms in individual participants. In this observational study among 21 participants, age 7-16 years, we performed a replicated time-series analysis of symptom fluctuations in asthma and/or allergic rhinitis and ADHD. Data were collected through parents who filled in a daily online questionnaire during up to 50 days. In each individual, we investigated the temporal order of fluctuations in atopic disease symptoms and ADHD symptoms using a vector autoregressive (VAR) model while using sleep problems and medication use as covariates. For 16 out of 21 participants, we constructed a VAR model. For a majority of the participants, significant associations were detected between atopic disease symptoms and ADHD symptoms. The results were heterogeneous; the direction, sign, and timing of the relationship between ADHD, atopy, sleep problems, and medication use varied between individuals. This study provides additional evidence that the symptom expression of atopy and ADHD are related. However, the connection between both diseases in children is found to be heterogeneous within our study population.

Potential normalization of an asthma mHealth intervention in community pharmacies: Applying a theory-based framework.

BACKGROUND: Effective mobile health (mHealth) interventions have been developed to support patients with their medication use, however to date few are widely used in pharmacy practice. Normalization of an intervention is essential to have a population impact, which is defined as 'the process of getting a new intervention into routine practice'. OBJECTIVE: The aim of this study was to assess the normalization potential of a complex mHealth intervention for adolescents with asthma (ADolescent Adherence Patient Tool; ADAPT) in community pharmacy practice. METHODS: The Normalization Process Theory (NPT), a sociological action theory, was retrospectively applied to study the normalization potential of ADAPT. NPT explains factors that promote or hinder implementation, embedding, and integration of new interventions in clinical practice. Evaluation data (structured interviews and questionnaires) of 23 pharmacists who used the ADAPT intervention were used for this study. RESULTS: Pharmacists understood the purpose of the ADAPT intervention and were prepared to undertake the necessary work of implementation. However changes at different levels are needed to support full normalization, such as changes in the intervention itself and changes in the pharmacist's work flow. The potential for normalization could also be enhanced by the use of product champions and appropriate reimbursement guidelines, to ensure uptake of the intervention by other pharmacists. Support from professional bodies for the use of mHealth could also promote normalization. CONCLUSIONS: Normalization of mHealth is a complex continuous process. The ADAPT intervention has the potential to be normalized in community pharmacy practice, but full normalization would require changes in both daily pharmacy practice and reimbursement models.

Asthma control and quality of life in adolescents: The role of illness perceptions, medication beliefs, and adherence.

Objective: Asthma control and quality of life (QoL) are important disease outcomes for asthma patients. Illness perceptions (cognitive and emotional representations of the illness) and medication beliefs have been found to be important determinants of medication adherence, and subsequently disease control and QoL in adults with asthma. In adolescents, this issue needs further elucidation. Therefore, the aim of this study was to explore the relationship between illness perceptions, medication beliefs, medication adherence, disease control, and QoL in adolescents with asthma.Methods: In this cross-sectional study, we used baseline data of adolescents with asthma (age 12-18 years) who participated in the ADolescent Adherence Patient Tool (ADAPT) study. Questionnaires were administrated online, and included sociodemographic variables and validated questionnaires measuring self-reported illness perceptions, medication beliefs, medication adherence, disease control, and QoL.Results: Data of 243 adolescents with asthma were available; age 15.1 ± 2.0 years and 53% females. More than half of these adolescents (62%; n = 151) reported to be non-adherent (Medication Adherence Report Scale ≤23) and 77% (n = 188) had uncontrolled asthma. There was a strong positive correlation between disease control and QoL (r = 0.74). All illness perceptions items were correlated with disease control and QoL, with the strongest correlation between 'identity' (symptom perception) and QoL (r=-0.66). Medication adherence was correlated to medication beliefs (r = 0.38), disease control (r = 0.23), and QoL (r = 0.14), whereas medication beliefs were only associated with adherence.Conclusions: Stimulating positive illness perceptions and medication beliefs might improve adherence, which in turn might lead to improved disease control and better QoL.

[Medication use during pregnancy and lactation; urgent need for one independent source of information]. / Medicatiegebruik tijdens zwangerschap en lactatie.

It is important for healthcare professionals and pregnant women to have knowledge of the risks of using medicines during pregnancy and lactation. This not only concerns the influence of the medicinal product on the pregnant woman and the pregnancy, but also its impact on the growth and development of the (unborn) child, neonatal adaptation, possible precautions regarding child-birth, drug excretion in breast milk, and the short-term and long-term consequences for the newborn child. At present, information and advices are often fragmentary, sometimes contradictory, not easily accessible, or even not available at all. It is high time for one independent source to provide unambiguous, scientifically substantiated information and advice, accessible to both healthcare professionals and pregnant women - preferably in a digital format.