2016, Vol 12, No 4
Safety of pharmacotherapy in children in the context of developmental differences
Pediatr Med Rodz 2016, 12 (4), p. 363–374
DOI: 10.15557/PiMR.2016.0036

Physiological changes during development of neonates, infants and children affect pharmacokinetic and pharmacodynamic properties of many drugs. The immaturity of the organism and its considerable changes over time strongly affect absorption, distribution, biotransformation and excretion of drugs, and thus their efficacy and safety. Children, particularly under 4 years of age, are susceptible to a range of adverse effects observed in adults, but they can also develop additional reactions due to direct drug toxicity on the developing organs. However, only scarce evidence exists on the action of drugs in children since most pharmacokinetic and pharmacodynamic studies have been conducted in adults. In the United States and European Union, also in Poland, off-label and unlicensed use of drugs are allowed and commonly practised, mainly in hospitalised children. This means that a drug can be used in a different way than described in the Summary of Product Characteristics, e.g. doses or intervals between them can be changed, the drug can be used for different indications, the route of administration or age range can be different, etc. The rationale underlying such actions is the necessity of saving life or health or inefficacy of previous treatment. It is estimated that 25–89% of hospitalised children and 69–100% of newborns treated in neonatal intensive care units worldwide have received at least one drug in the off-label manner or as an unlicensed product. Studies and reports on pharmacovigilance have shown that adverse drug reactions in children after off-label use are an important problem. As a response to such signals, the European Medicines Agency issued certain legislative changes in 2007 to enable clinical trials in children and to develop paediatric formulations of drugs, particularly for neonates. The article discusses age-related differences in absorption, distribution, biotransformation and excretion of drugs depending on the route of administration as well as problems associated with off-label and unlicensed use of drugs and adverse effects of drugs in children.

Keywords: infant, developmental differences, pharmacokinetics, off-label and unlicensed drug use, adverse effects
The preparation of patients taking anticoagulants for endoscopic procedures
Pediatr Med Rodz 2016, 12 (4), p. 375–383
DOI: 10.15557/PiMR.2016.0037

Drugs that inhibit platelet aggregation and anticoagulants are widely used in primary and secondary prevention of thromboembolism and treatment of venous thrombosis. The use of these drugs is associated with an increased risk of bleeding during an endoscopic procedure, and their discontinuation leads to an increased risk of a thromboembolic event. The paper presents how to assess risk and how to prepare a patient treated with antiplatelet or anticoagulant drugs for endoscopic procedures. In each case, one should consider indications and planned duration of treatment as well as urgency of the procedure. Diagnostic gastroscopy and colonoscopy do not usually require treatment modification, while the procedures with increased risk of bleeding require a change in therapy. In the case of antiplatelet drugs, it may be needed to stop it at a proper time before endoscopy. In the case of a dual antiplatelet therapy, when there are absolute indications for its use, one should consider postponing the procedure. Patients with increased risk of bleeding, treated with vitamin K antagonists, should have the treatment temporarily stopped and replaced with a bridging therapy with low molecular weight heparin; if the thromboembolic risk is assessed as low, a bridge therapy is not needed. The time to suspend the use of oral anticoagulants which are non-vitamin K antagonists depends on the risk of bleeding and renal function. Decisions concerning treatment may require consultation of a specialist ordering the anticoagulant or antiplatelet therapy as well as the opinion of an endoscopy centre in which the procedure is to be conducted. The doctor performing the examination should be informed about the treatment used by the patient and its modification.

Keywords: anticoagulant therapy, gastroscopy, colonoscopy, antiplatelet therapy, oral anticoagulants
Prevention of hearing loss in children up to 7 years of age
Pediatr Med Rodz 2016, 12 (4), p. 384–393
DOI: 10.15557/PiMR.2016.0038

Hearing impairment can be classified based on various criteria. Each of these criteria provides information on the cause as well as characterises the impairment in terms of parameters needed for prevention, diagnosis and further treatment. The main criteria for the classification of hearing disorders include aetiology, location, age of onset and the depth of hearing loss. Hearing impairment is currently a very important social problem and one of the most common developmental disorders. Hearing impairment often occurs at birth. Statistics show that 2–3 children per 1,000 births are affected by the disorder, therefore prevention is essential. It allows to prevent hearing loss, or at least reduce its impact on the further life of an individual. This paper describes the classification of hearing impairment in children. The aim was to present measures for the prevention of hearing defects in children up to seven years old. The used research method was a 1998–2014 literature review. Phase 1 prevention, which includes activities undertaken by expectant mothers, should be used to prevent the risk of hearing impairment in children in this age group. Phase 2 prevention (the Universal Neonatal Hearing Screening) is the most common and effective strategy. Phase 3 prevention in children with hearing impairment involves the use of a hearing aid or implant. Avoiding ear infections is a less invasive, although sometimes insufficient, method.

Keywords: hearing impairment, children, audiology, prevention
Bean – an important element of a healthy diet. Nutritional values analysis
Pediatr Med Rodz 2016, 12 (4), p. 394–403
DOI: 10.15557/PiMR.2016.0039

Legumes are a rich source of various nutrients. In the Polish culture, one of the varieties of beans has a special significance. Due to the appearance of seeds – on the bright seeds there are dark red spots in the shape of the Piast eagle – at the times of annexation, it was recognised as a symbol of patriotism. Cultivation was therefore banned then by the authority. Today, this bean variety was entered on the list of traditional products in Poland. Bean in Poland is one of the twelve Christmas Eve dishes. Health benefits of legumes have been known since the ancient times in many countries. Anticancer properties are due to the presence of enzymes which affect the division, differentiation, and apoptosis cells in the body. Rich in phytoestrogens, especially isoflavones, they protect women against the development of hormone-dependent cancers and reduce the symptoms associated with menopause. Rich in fibre, they regulate the motility of the gastrointestinal tract and have prebiotic properties. They also reduce insulin resistance in type 2 diabetes. By influencing the expression of genes involved in β-oxidative fats and gluconeogenesis, lipogenesis, they reduce triglyceride levels, LDL cholesterol and increase the levels of HDL cholesterol. Moreover, they help to maintain a normal body weight and reduce high blood pressure. It is therefore recommended particularly for people suffering from the metabolic syndrome or predisposed to its occurrence. It is advised to increase the content of legumes in our diet because of the health benefits and taste.

Keywords: health, legumes, Poland, beans, nutrition
The impact of the microbiota on human health
Pediatr Med Rodz 2016, 12 (4), p. 404–412
DOI: 10.15557/PiMR.2016.0040

The term “microbiota” refers to microorganisms that colonise a given ecological niche. Recent studies in the field of molecular biology have provided at least partial insight into complex interactions between microorganisms themselves and between the microflora and host organism. Particularly favourable conditions for bacteria to proliferate are found in the large intestine, mainly due to slow intestinal passage. The weight of the systemic microbiota is estimated at even 2 kg. Despite such a numerous and diversified commensal flora, no inflammatory reactions are elicited since there are numerous mechanisms that protect against excessive proliferation of commensal bacteria and their penetration beyond the gastrointestinal tract. The microbiota has various significant functions in the organism. For instance, it enables effective energy assimilation, participates in vitamin synthesis, magnesium, calcium and iron ion absorption and strengthens intestinal integrity. By occupying the niche and stimulating the immune system, it protects from the proliferation of potential pathogens. The relationship of the microbiome with specific disease entities has been recently underlined. Studies on the intestinal flora composition in patients with gastrointestinal diseases, such as non-specific inflammatory bowel disease, have delivered important information. It has been suggested that there is a relationship between the commensal flora composition and obesity, allergy, cancer or autism. The human microbiome undergoes various changes in response to external and internal factors. The most abrupt disorders are called dysbiosis. Its major causes include antibiotic therapy with its unfavourable influence on the human organism that can persist for several months or even years.

Keywords: microbiome, microbiota, dysbiosis, antibiotic therapy
Infantile colic
Pediatr Med Rodz 2016, 12 (4), p. 413–418
DOI: 10.15557/PiMR.2016.0041

Infantile colic is one of the most common functional gastrointestinal disorders in infants, usually occurring between 2 weeks to 4 months of age. According to the definition, infantile colic is characterised by episodes of inconsolable crying, generally observed in the evening. Although these symptoms usually resolve spontaneously in the first six months of life, they often cause parental anxiety, leading to repeated medical appointments in search for help. Despite 40 years of research, the causes of this disorder are still unclear; hypersensitivity to cow’s milk protein, lactose intolerance, impaired gut microbiota, immaturity of the nervous system, the negative impact of tobacco smoke, inappropriate childcare techniques and psychosocial factors are believed to be involved in the pathogenesis. The treatment involves behavioural methods, i.e. reducing infant exposure to external stimuli. Breastfeeding mothers are advised to eliminate caffeine and hot spices from their diet and, in some cases, switch to a dairy-free diet. For formula-fed infants, it is recommended to use hydrolysates with a high degree of hydrolysis. Simethicone is commonly used in the pharmacological treatment as it reduces the surface tension of intestinal gases, enabling their easier elimination. The Rome III Diagnostic Criteria recommend to appropriately continue any method if considered effective by the parents, provided that there are no harmful consequences.

Keywords: infantile colic, infants, diagnostics, treatment
Nutrition status and 24-hour blood pressure parameters in hospitalised adolescents with primary hypertension
Pediatr Med Rodz 2016, 12 (4), p. 420–427
DOI: 10.15557/PiMR.2016.0042

The occurrence of overweight and obesity in children and adolescents can be associated with increased incidence of hypertension in this population. Aim of the study: Assessment of the relationship between 24-hour blood pressure parameters in hospitalised teenagers with primary hypertension and their nutrition status at the stage of diagnosis. Material and methods: The study group consisted of 112 patients aged 11–17 years (42 girls and 70 boys) with diagnosed primary hypertension. Nutrition indicators were taken into account. The study group was divided into group I – persons with normal nutrition status (40 patients) and group II – persons with overweight/obesity (72 patients). The groups were compared using the t-test with a separate variance estimation or with the Mann–Whitney U test. The relationship between blood pressure parameters and nutrition status indicators was assessed based on Spearman’s rank correlation. Results: The study groups were significantly different in terms of the nutrition status indicators, but no significant differences were observed in the evaluated blood pressure parameters. The nutrition status indicators in group I were not significantly correlated with the blood pressure parameters. Significant correlations were found in group II. Positive correlation with the nutrition indicators were observed for nocturnal systolic blood pressure load and average nighttime value of this load. Body mass index exhibited a negative correlation with nocturnal systolic load decline. Conclusions: 1) 24-hour blood pressure parameters in hospitalised adolescents with primary hypertension that correlated with the nutrition status include nighttime systolic blood pressure parameters (nocturnal load, mean measure, nocturnal fall). 2) The relationship of these parameters with the nutrition status was observed only in patients with overweight/obesity.

Keywords: adolescents, hypertension, nutrition status, 24-hour blood pressure monitoring, hospitalisation
Metabolic profile and dietary fructose intake in prehypertensive and hypertensive adolescents
Pediatr Med Rodz 2016, 12 (4), p. 428–435
DOI: 10.15557/PiMR.2016.0043

Introduction: Primary prevention of hypertension underlines the relevance of body composition abnormalities, particularly of so-called lean body mass. Increased fructose intake can lead to elevated blood pressure. Aim: The aim of this study was to assess the metabolic profile and dietary fructose intake in prehypertensive and hypertensive adolescents. Material and methods: Thirty-one patients (18 boys and 13 girls) aged 12–18 years (median: 15 years) with well controlled hypertension and prehypertension were selected for the study. The authors measured body height and weight, body mass index, waist-to-hip ratio, waist-to-height ratio as well as fat content and lean body mass using bioelectrical impedance analysis. The patients’ diet was assessed in terms of fructose intake and food energy value. Results: Forty-two per cent of children (33% of boys and 61% of girls) had abnormally high body mass index (BMI z-score > 2.0 SDS). The waist-to-height ratio was significantly higher in girls than in boys (0.53 and 0.45, respectively, p = 0.04). The results in waist circumference z-score were similar (2.82 vs. 1.13, respectively, p = 0.02). Girls had greater fat mass than boys (31% vs. 17%, respectively, p = 0.001). The energy value of girls’ diet was lower (1,967 vs. 2,683 kcal, p = 0.003), but excessive energy intake was observed in both groups (120% of requirement). Dietary fructose intake covered 11% of energy requirement. Conclusions: The study demonstrated that girls with elevated blood pressure have a greater amount fat tissue than boys and its distribution is more unfavourable. The diet of children with elevated blood pressure values is characterised by excessive energy delivery, and dietary fructose intake exceeds daily recommended intake of simple sugars.

Keywords: arterial hypertension, fructose, adolescents, body composition
Contrast-induced acute kidney injury in children with cardiovascular defects – results of a pilot study
Pediatr Med Rodz 2016, 12 (4), p. 436–444
DOI: Pediatr Med Rodz 2016, 12 (4), p. 436–444

Introduction: Contrast-induced nephropathy – acute kidney injury is an acquired kidney injury that is an important factor in short- and long-term cardiovascular complications. Contrast-induced nephropathy – acute kidney injury continues to be diagnosed based on serum creatinine level. Serum creatinine, however, is a delayed indicator of contrast-induced nephropathy, as its levels typically peak between 1 and 3 days following contrast exposure. Currently, more sensitive biomarkers of kidney injury are sought, with human neutrophil lipocalin (also known as neutrophil gelatinase-associated lipocalin) highlighted in literature as a troponin-like biomarker of early nephropathy. Aim of the study: Changes in serum and urine neutrophil gelatinase-associated lipocalin levels were assessed in children with congenital heart diseases, following a scheduled cardiac catheterization procedure. Material and methods: The group studied comprised 16 patients. The neutrophil gelatinaseassociated lipocalin and creatinine levels, along with urine and serum neutrophil gelatinase-associated lipocalin/creatinine ratio were evaluated five times at different time intervals from the procedure. The group did not vary in respect of kidney function, preprocedure management, and volume expansion (hydration therapy) prior to the procedure. Results: In the assessed material, median neutrophil gelatinase-associated lipocalin rose as early as 2 hours after exposure to contrast as compared with baseline [median = 28.2 ng/mL (Quartile 1 = 22.8 – Quartile 3 = 33.77) vs. median = 25.87 ng/mL (Quartile 1 = 19.4 – Quartile 3 = 29.6)]. Serum neutrophil gelatinase-associated lipocalin level peaked in hour 6 of our study: median – 30.6 ng/mL (Quartile 1 = 22.32 – Quartile 3 = 42.17), then reverting to normal. Urine neutrophil gelatinaseassociated lipocalin peaked in hour 24 of the study, subsequently dropping below baseline in hour 48. Glomerular filtration was slightly impaired between hour 2 and 6, and later improvement of estimated glomerular filtration rate was noted. Conclusions: The analysis of the obtained results indicates the usefulness of measuring neutrophil gelatinase-associated lipocalin level for the diagnosis of early contrast-induced nephropathy – acute kidney injury in paediatric patients. Contrastinduced nephropathy – acute kidney injury biomarkers in such clinical circumstances elevate as early as 2 hours after intravenous administration of contrast agents.

Keywords: contrast-induced nephropathy – acute kidney injury, congenital heart defects, angiography, neutrophil gelatinase-associated lipocalin
Can mild abdominal pain be the only sign of developing Crohn’s disease? A case report
Pediatr Med Rodz 2016, 12 (4), p. 445–450
DOI: 10.15557/PiMR.2016.0045

Crohn’s disease is a condition of multifactorial unclear aetiology and increasing incidence. It can involve any fragment of the gastrointestinal tract and considerably deteriorates quality of life. Typical symptoms include: abdominal pain, chronic diarrhoea with mucus and/or blood, palpable, frequently tender resistance in the abdominal cavity, weight loss, weakness, subfebrile/febrile temperature and perianal changes. Approximately 30% of children with this disease manifest symptoms that are not associated with the gastrointestinal tract, such as growth delay, joint pain, ocular changes and skin lesions. A diversified and sometimes atypical clinical course can pose a number of diagnostic difficulties, delay diagnosis and, consequently, increase the risk of complications, which is of particular significance in patients of developmental age. The aim of this paper is to present a patient who, during the diagnosis for Crohn’s disease, presented a disproportion between very few clinical symptoms and considerable severity of inflammatory changes on endoscopy. The shrewd attitude of the first contact physician enabled a rapid diagnosis and implementation of proper treatment.

Keywords: Crohn’s disease, diagnosis, symptoms, children
Cat scratch disease in a 8-year-old boy – a case report
Pediatr Med Rodz 2016, 12 (4), p. 451–454
DOI: 10.15557/PiMR.2016.0046

Cat scratch disease is a rare infectious disease caused by the Gram-negative bacterium Bartonella henselae. Most often, it affects children and adolescents. Infection occurs primarily through bites or scratches by a cat, or less commonly a dog, rabbit or guinea pig. It is transmitted also by body lice and cat fleas. It most often occurs in the form of local lymphadenopathy, in individual cases there may be symptoms of generalised disease. The paper presents a case report of an early diagnosed and confirmed by serological tests cat scratch disease in an 8-year-old boy. The symptoms in the form of painful inguinal lymphadenopathy were observed 3 weeks after the boy sustained a cat scratch in the navel area. Except for a slightly accelerated erythrocyte sedimentation rate, the laboratory findings were normal. After 10-day hospitalisation, improvement of the patient’s overall condition and a significant reduction in lymph nodes size were achieved, and the pain was eliminated. Cat scratch disease is correctly diagnosed increasingly often, yet it still frequently poses a diagnostic problem.

Keywords: cat scratch disease, lymphadenopathy, Bartonella henselae, children
Paediatric triage system at the Emergency Department of the Western Hospital in Grodzisk Mazowiecki, Poland
Pediatr Med Rodz 2016, 12 (4), p. 457–465
DOI: 10.15557/PiMR.2016.0047

The word triage comes from the French verb trier, which means to separate from others, to sort. There are a number of prehospital triage systems in the world, usually designed for adult patients. Triage systems for children have also been developed, such as JumpSTART MCI Triage, Paediatric SATS Chart or Paediatric CTAS. Poland lacks an appropriate uniform paediatric system and paediatric hospitals use systems from other countries. Until recently no method of prioritising and coding of sick children reporting to the hospital had been developed. Such an attempt has been made at the Western Hospital in Grodzisk Mazowiecki, Poland, where an original paediatric triage system has been created to meet the needs of the emergency department. This article presents the paediatric triage system of the Western Hospital in Grodzisk Mazowiecki, which has been used since April 2016. This system for categorisation and prioritisation of patients was developed based on the Manchester Triage System. It uses the following colours: red – for patients requiring immediate help, orange – for children requiring urgent admission within 10 minutes, yellow – for patients who may wait for help up to 1 hour, green – for individuals who may receive help within up to 4 hours and blue – for patients who can wait up to 6 hours. A fast-track procedure has also been included. The triage system is an additional procedure that does not cause any inconvenience and thanks to which the patient may receive necessary help as quickly as their clinical condition requires it. In addition, full documentation of the procedure protects medical staff against unjustified claims by the guardians of sick children.

Keywords: paediatric triage, patient prioritisation, emergency department, life-threatening medical emergencies, children
Impact of selected construction elements of capsule-based dry powder inhalers on the manner of drug delivery to the lungs
Pediatr Med Rodz 2016, 12 (4), p. 466–470
DOI: 10.15557/PiMR.2016.0048

The article discusses selected issues related to construction and performance of dry powder inhalers with the spinning capsule: Aerolizer® and cyclohaler. Investigations involved devices and capsules found among medicinal products available on the domestic market. Based on scanning electron microscope images, the following were determined: (i) shape and crosssection of needles used to puncture drug-containing capsules as well as (ii) size, geometry and cross-section of small holes in the capsules through which powder is introduced into the airstream while using the inhaler. It was found that differences in shape and spatial arrangement of needles affect both the total area of holes and the character of perforation. In Aerolizer® inhalers, the average area of holes is 1.3 mm2 at each side of the capsule, and oval through holes are obtained. In investigated cyclohaler-type inhalers, the average hole area ranges from 1.6 to 2.2 mm2, and perforations are partly covered by torn fragments of the capsule. It has been determined that both the type of needles and inherent properties of the material from which capsules are made have an impact on observed effects. The authors have also assessed the potential influence of differences in the manner of perforation and applied capsule material on even powder release and aerosol generation in the device. Also, attention has been paid to other significant features of inhaler devices and powder formulations which decide about effective inhalation drug delivery to the respiratory system.

Keywords: inhalation drugs, aerosol, dry powder inhaler, capsule