Self-medication among children and adolescents in Germany: results of the National Health Survey for Children and Adolescents (KiGGS)

AIMS

Despite the widespread use of self-medication among the child population and the potential harm it can do, up-to-date epidemiological data on self-medication are sparse worldwide. The aim was to investigate the prevalence and correlates of self-medication use among non-institutionalized children in Germany, focusing on the paediatric self-medications that are most frequently used.

METHODS

All cases of last-week medicine use were recorded among 17 450 children aged 0–17 years who participated in the 2003-2006 German Health Interview and Examination Survey for Children and Adolescents. Self-medication was defined as the use of medicines that had either been bought over the counter or obtained from other sources (OS). The complex sample method was used to estimate the prevalence of, and factors associated with self-medication use.

RESULTS

During the previous week 25.2% of participants had used self-medication (17.0% used over-the-counter drugs and 9.9% other-sources drugs). Self-medication accounted for 38.5% of total medicine use and included all medication classes. These clustered among drugs acting on the respiratory system (32.1%), alimentary tract and metabolism (21.6%), skin (14.2%) and nervous system (11.3%), as well as homoeopathic preparations (8.6%). Vitamin preparations were most frequently used with a weighted user prevalence of 4.7% (5.2% vs. 4.1%, P < 0.001, boys vs. girls), followed by cough and cold medicines (CCMs) 4.4% (4.3 vs. 4.5, P > 0.05) and analgesics 3.7% (3.0% vs. 4.4%, P < 0.001, both boys vs. girls). Overall use of aspirin among children <12 years old was 0.3%; use of CCMs was substantial (4.4%), particularly among children <6 years old. Use of self-medication was closely related to older adolescent ages of between 14 and 17 years (odds ratio 1.16; 95% confidence interval 1.00, 1.33), children with a poor health status (1.29; 1.10, 1.52), with no immigration background (1.55; 1.33, 1.80), from families with a higher household income (1.23; 1.06, 1.42) and with mothers with a higher educational level (1.37; 1.19, 1.57).

CONCLUSIONS

Self-medication use is highly prevalent in Germany, particularly among children and adolescents from families with a higher socioeconomic status. Self-medication in younger children using such drugs as CCMs and aspirin suggested inappropriate drug use and potential risks. This should be closely monitored and warrants an education programme for parents in Germany.     

Assessment of antitussive efficacy of dextromethorphan in smoking related cough: objective vs. subjective measures

AIMS

Using an established model of smokers cough we measured the antitussive effects of dextromethorphan compared with placebo.

METHODS

The study was a randomized, double-blind placebo controlled, crossover comparison of 22 mg 0.8 ml⁻¹ dextromethorphan delivered pregastrically with matched placebo. Objective and subjective measurements of cough were recorded. Subjective measures included a daily diary record of cough symptoms and the Leicester quality of life questionnaire. Cough frequency was recorded using a manual cough counter. The objective measure of cough reflex sensitivity was the citric acid, dose–response cough challenge.

RESULTS

Dextromethorphan was significantly associated with an increase in the concentration of citric acid eliciting an average of two coughs/inhalation (C2) when compared with placebo, 1 h post dose by 0.49 mM (95% CI 0.05, 0.45, geometric mean 3.09) compared with placebo 0.24 mM (geometric mean 1.74) P < 0.05 and at 2 h 0.57 mM (95% CI 0.01, 0.43, geometric mean 3.75) compared with placebo 0.34 mM (geometric mean 2.19) P < 0.05). There was a highly significant improvement in the subjective data when compared with baseline. However, there was no significant difference between placebo and active treatment. No correlation was seen between cough sensitivity to citric acid and recorded cough counts or symptoms. When both subjective and objective data were compared with screening data there was evidence of a marked ‘placebo’ effect.

CONCLUSIONS

The objective measure of cough sensitivity demonstrates dextromethorphan effectively diminishes the cough reflex sensitivity. However, subjective measures do not support this. Other studies support these findings, which may represent a profound sensitivity of the cough reflex to higher influences.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Dextromethorphan is widely used as a cough suppressant in over the counter medications.
• Its efficacy in altering cough reflex sensitivity has been shown in healthy volunteers. In contrast evidence for an effect on clinically important cough is poor.

WHAT THIS STUDY ADDS

• A significant decrease in evoked cough was seen with dextromethorphan compared with placebo. However, both placebo and active treatment improved subjective data to a similar degree.
• We doubt the validity of currently used objective tests in the investigation of antitussives.

     

Public awareness and views on unlicensed use of medicines in children

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• There is increasing concern about the use of those medicines in children which have not been fully studied and licensed for childhood use. Such use is not uncommon, due in large part to a lack of availability of fully licensed products and formulations that are suitable for children.
• There is little published information on the views of the public on this important area of paediatric care.

WHAT THIS STUDY ADDS

• A survey of 1000 members of the public in Northern Ireland indicated that such use of medicines in children is not well known.
• However, when informed about this practice, the majority believed that it would compromise safety and increase the likelihood of adverse effects. They also believed that parents/guardians should be told if their child was prescribed a medicine that had not been fully tested in children.
• Participants in the survey indicated that they would be reluctant to involve their child in a clinical trial to help with the licensing process unless the child was suffering from a life-threatening illness.

AIMS

To explore awareness and views of the general public on unlicensed use of medicines in children and on the participation of children in clinical trials.

METHODS

Members of the public completed a questionnaire survey administered by face-to-face interview in public areas in N. Ireland. The main outcome measures were the views on unlicensed use of medicines in children and on clinical trials in children.

RESULTS

One thousand participants (59.2% female) took part; 610 were parents. Most participants (86%) had no previous knowledge about unlicensed use of medicines in children. Being a parent did not influence this nor did being a parent of a child who suffered from a health problem (P > 0.05). Most participants (92%) felt that parents should be told about unlicensed use of medicines, with the doctor most frequently selected as the person who should inform parents. At the outset, only 1.8% of participants felt that the use of medicines in children was unsafe. However, having been informed about unlicensed use of medicines, this proportion increased dramatically (62.4%; P < 0.001). Views on whether participants would enter a child of their own into a clinical trial varied according to the health status of the child (P < 0.05) i.e. a child in good health (3.9%) vs a child with a life-threatening condition (41.9%).

CONCLUSIONS

There is limited public knowledge of unlicensed use of medicines in children and a general reluctance to involve children in clinical trials unless the child to be involved has a life-threatening condition.     

Access to orphan drugs despite poor quality of clinical evidence

AIM

We analysed the Belgian reimbursement decisions of orphan drugs as compared with those of innovative drugs for more common but equally severe diseases, with special emphasis on the quality of clinical evidence.

METHODS

Using the National Health Insurance Agency administrative database, we evaluated all submitted orphan drug files between 2002 and 2007. A quality analysis of the clinical evidence in the orphan reimbursement files was performed. The evaluation reports of the French ‘Haute Autorité de Santé’, including the five-point scale parameter ‘Service Médical Rendu (SMR), were examined to compare disease severity. Chi-squared tests (at P < 0.05 significance level) were used to compare the outcome of the reimbursement decisions between orphan and non-orphan innovative medicines.

RESULTS

Twenty-five files of orphan drugs and 117 files of non-orphan drugs were evaluated. Twenty-two of 25 (88%) submissions of orphan drugs were granted reimbursement as opposed to 74 of the 117 (63%) non-orphan innovative medicines (P = 0.02). Only 52% of the 25 orphan drug files included a randomized controlled trial as opposed to 84% in a random control sample of 25 non-orphan innovative submissions (P < 0.01). The duration of drug exposure was in most cases far too short in relation to the natural history of the disease.

CONCLUSIONS

Orphan drug designation predicts reimbursement despite poor quality of clinical evidence. The evidence gap at market authorization should be reduced by post-marketing programmes, in which the centralized regulatory and the local reimbursement authorities collaborate in an efficient way across the European Union member states.     

Altered xanthine oxidase and N-acetyltransferase activity in obese children

AIMS

It is well established that oxidative and conjugative enzyme activity differs between obese and healthy-weight adults. However, the effect of obesity on drug metabolism in children has not been studied extensively. This study examined whether obese and healthy-weight children vary with respect to oxidative enzyme activity of CYP1A2, xanthine oxidase (XO) and conjugative enzyme activity of N-acetyltransferase 2 (NAT2).

METHODS

In vivo CYP1A2, XO and NAT2 activity was assessed in obese (n = 9) and lean (n = 16) children between the ages of 6–10 years using caffeine (118.3 ml Coca Cola®) as probe. Urine samples were collected in 2-h increments over 8 h. Caffeine and metabolites were measured using LC/MS, and urinary metabolic ratios were determined based on reported methods.

RESULTS

Sixteen healthy-weight and nine obese children were evaluated. XO activity was elevated in paediatric obese volunteers compared with non-obese paediatric volunteers (XO metabolic ratio of 0.7 ± 0.06 vs. 0.6 ± 0.06, respectively, 95% CI 0.046, 0.154, P < 0.001). NAT2 activity was fivefold higher in the obese (1 ± 0.4) as compared with non-obese children (0.2 ± 0.1), 95% CI 0.26, 1.34, P < 0.05. However, no difference was observed in CYP1A2 activity between the groups (95% CI −2.72, 0.12, P > 0.05).

CONCLUSIONS

This study provides evidence that obese children have elevated XO and NAT2 enzyme activity when compared with healthy-weight controls. Further studies are needed to determine how this may impact the efficacy of therapeutic agents that may undergo metabolism by these enzymes.     

Adverse drug reactions in adult medical inpatients in a South African hospital serving a community with a high HIV/AIDS prevalence: prospective observational study

Aims

To describe the frequency, nature and preventability of community-acquired and hospital-acquired adverse drug reactions (ADRs) in a South African hospital serving a community with a high prevalence of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome.

Methods

A 3-month prospective observational study of 665 adults admitted to two medical wards.

Results

Forty-one (6.3%) patients were admitted as a result of an ADR and 41 (6.3%) developed an ADR in hospital. Many of the ADRs (46.2%) were considered preventable, although less likely to be preventable in HIV-infected patients than in those with negative or unknown HIV status (community-acquired ADRs 2/24 vs. 35/42; P < 0.0001; hospital-acquired ADRs 3/25 vs. 14/26; P = 0.003). Patients admitted with ADRs were older than patients not admitted with an ADR (median 53 vs. 42 years, P = 0.003), but 60% of community-acquired ADRs at hospital admission were in patients <60 years old. Among patients <60 years old, those HIV infected were more likely to be admitted with an ADR [odds ratio (OR) 2.32, 95% confidence interval (CI) 1.17, 4.61; P = 0.017]. Among HIV-infected patients, those receiving antiretroviral therapy (ART) were more likely to be admitted with an ADR than those not receiving ART (OR 10.34, 95% CI 4.50, 23.77; P < 0.0001). No ART-related ADRs were fatal. Antibiotics and drugs used for opportunistic infections were implicated in two-thirds of hospital-acquired ADRs.

Conclusions

ADRs are an important, often preventable cause of hospitalizations and inpatient morbidity in South Africa, particularly among the elderly and HIV-infected. Although ART-related injury contributed to hospital admissions, many HIV-related admissions were among patients not receiving ART, and many ADRs were associated with medicines used for managing opportunistic infections.

What is already known about this subject

• Studies conducted primarily in developed countries have shown that adverse drug reactions (ADRs) are a significant cause of hospital admission, prolong hospital stay and consequently increase the cost of disease management in patients.
• Cardiovascular medicines, hypoglycaemic agents, nonsteroidal anti-inflammatory drugs and antibiotics are the most frequently implicated medicines in these studies.
• A large proportion of these ADRs have been shown to be preventable through improved drug prescribing, administration and monitoring for adverse effects.

What this paper adds

• This is the first Sub-Saharan African study in the HIV/AIDS era that describes the contribution of ADRs to patient morbidity, hospitalisation and mortality.
• Cardiovascular medicines and antiretroviral therapy contributed the most to community-acquired ADRs at the time of hospital admission while medicines used for opportunistic infections (such as antifungals, antibiotics and antituberculosis medicines were most frequently implicated in hospital acquired ADRs.
• ADRs in HIV-infected patients were less likely to be preventable.

     

Pulse pressure amplification in relation to body fatness

AIMS

Arterial pressure transfer to the periphery is accompanied by pulse pressure amplification (PPA). Pulse pressure is influence by body fat. The purpose of the present study was to evaluate any possible inter-relation between body fatness and PPA in healthy subjects.

METHODS

Haemodynamic and wave reflection indices were estimated by pulse wave analysis. Body fat was measured by bio-impedance.

RESULTS

A total of 367 healthy volunteers (136 men and 231 women) was studied. Pulse pressure amplification correlated significantly with percentage of body fat (r = −0.53, P < 0.0001), age (r = −0.62, P < 0.0001), height (r = 0.43, P < 0.0001), heart rate (r = 0.28, P < 0.0001) and mean blood pressure (r = −0.29, P < 0.0001). The association of PPA with body fat was also significant in a multiple linear regression model. Age was an independent predictor of PPA and analysis of study subjects subdivided into two groups, those <50 years and those >50 years showed that body fatness correlated inversely and significantly with PPA in individuals both younger and older than 50 years (r = −0.44, P < 0.0001, r = −0.37, P < 0.0001 respectively). Augmentation pressure was also associated significantly with percentage of body fat in both subgroups (r = 0.48, P < 0.0001 and r = 0.49, P < 0.0001 respectively).

CONCLUSIONS

This study performed on healthy subjects showed that pulse pressure amplification is related to body fatness over a wide age range. Percentage body fat is significantly associated with augmentation pressure, a component of central pulse pressure.     

High dose methotrexate chemotherapy: pharmacokinetics, folate and toxicity in osteosarcoma patients

AIMS

To investigate the relationships between pretreatment folate concentrations, MTX pharmacokinetics and acute toxicities following high dose methotrexate (HD MTX) therapy.

METHODS

MTX and its major extracellular metabolite 7-OH-MTX were measured in eight serum samples per HD MTX cycle in 65 consecutive osteosarcoma patients (288 cycles) and AUC (area under the blood concentration–time curve) was calculated. Pretreatment concentrations of folate in serum (S) and erythrocytes (ER) were determined. Hepatic, renal and haematological toxicities, assessed by routine laboratory parameters, as well as mucositis were graded according to National Cancer Institute Common Terminology Criteria for adverse events (CTCAE v.3.0). Dermatitis and pleuritis were reported as occurred or not.

RESULTS

S- and ER-folate pretreatment concentrations increased significantly with increasing number of HD MTX cycles (P < 0.001). ER-folate pretreatment concentrations were higher among males (median 610 nmol l⁻¹, 95% CI 550, 680) compared with females (median 465 nmol l⁻¹, 95% CI 430, 520, P < 0.001), but showed no correlation with MTX or 7-OH-MTX pharmacokinetics. We found correlations between alanine aminotransferase peak concentration (ALAT_max) and clearance of MTX (P < 0.001), gender (P < 0.001), age (P < 0.001) and 7-OH-MTX concentrations (P < 0.001), the latter being the main factor influencing ALAT_max.

CONCLUSION

Our results suggest that 7-OH-MTX is involved in the development of HD MTX hepatic toxicity and that young female patients are most affected.     

Superior palatability of crushed lercanidipine compared with amlodipine among children

AIMS

To compare the taste of equivalent doses of pulverized amlodipine and lercanidipine, two calcium channel blockers, among children with kidney disease.

METHODS

Each child received a test dose of 1 mg of amlodipine besylate and 2 mg of lercanidipine in a single-blinded fashion. Children indicated their preference by pointing to the appropriate face on a visual analogue scale (VAS) that depicts five degrees of pleasure.

RESULTS

The VAS palatability score assigned to lercanidipine was higher than that assigned to amlodipine both in nine children 4–7 years of age (P < 0.005) and in 10 children 8–11 years of age (P < 0.005). The preference for lercanidipine was statistically significant in both girls (P < 0.02) and boys (P < 0.001) and in both children initially presented amlodipine (P < 0.005) and children initially presented lercanidipine (P < 0.005).

CONCLUSIONS

There is a lack of appropriate formulations for children prescribed drugs originally designed for adults, such as calcium channel blockers. Parents therefore crush available tablets and administer the medication mixed with solid food or a palatable drink. From the perspective of the child, the taste of pulverized lercanidipine is superior to that of pulverized amlodipine.     

Orange and apple juice greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren

AIM

The aim of this study was to investigate the effects of orange juice and apple juice on the pharmacokinetics and pharmacodynamics of aliskiren.

METHODS

In a randomized crossover study, 12 healthy volunteers ingested 200 ml of orange juice, apple juice or water three times daily for 5 days. On day 3, they ingested a single 150-mg dose of aliskiren. Plasma aliskiren concentrations were measured up to 72 h, its excretion into urine up to 12 h and plasma renin activity up to 24 h.

RESULTS

Orange and apple juice reduced aliskiren peak plasma concentrations by 80% (95% CI 63%, 89%, P < 0.001) and 84% (95% CI 72%, 91%, P < 0.001), and the area under the plasma aliskiren concentration–time curve (AUC) by 62% (95% CI 47%, 72%, P < 0.001) and 63% (95% CI 46%, 74%, P < 0.001), respectively, but had no significant effect on its elimination half-life or renal clearance. The decreases in aliskiren AUC by orange and apple juice correlated with aliskiren AUC during the water phase (r = 0.98, P < 0.001). Plasma renin activity was 87% and 67% higher at 24 h after aliskiren during the orange juice and apple juice phases, respectively, than during the water phase (P < 0.05).

CONCLUSIONS

Orange juice and apple juice greatly reduce the plasma concentrations and renin-inhibiting effect of aliskiren, probably by inhibiting its OATP2B1-mediated influx in the small intestine. Concomitant intake of aliskiren with orange or apple juice is best avoided.     

Exploring epistatic relationships of NO biosynthesis pathway genes in susceptibility to CHD

Aim:

To assess the epistatic relationships of nitric oxide (NO) biosynthesis pathway genes in susceptibility to coronary heart disease (CHD).

Methods:

A total of 2142 subjects enrolled in two case-control studies was genotyped for 7 single-nucleotide polymorphisms (SNP) within NO biosynthesis pathway genes using TaqMan assays. The association analyses were performed at both SNP and haplotype levels. Two-way SNP-SNP interactions and high-order interactions were tested using multiple unconditional logistic regression analyses and generalized multifactor dimensionality reduction (GMDR) analyses, respectively.

Results:

Two alleles (rs1049255*C and rs841*A) were identified that were significantly associated with increased risk of CHD after adjusting for all confounders (OR=1.21, 95% CI: 1.06−1.39, combined P=0.001, P_corr=0.007 and OR=1.30, 95% CI 1.12−1.50, combined P<0.001, P_corr<0.001, respectively). Significant two-way SNP–SNP interactions were found between SNP rs2297518 and these two significant polymorphisms, affecting the risk of CHD (P<0.001 for both). No significant high-order interactions were identified.

Conclusion:

The results suggested that two-way SNP–SNP interactions of polymorphisms within NO biosynthesis pathway genes contribute to CHD risk.     

Association of serum omentin-1 levels with coronary artery disease

Aim:

Omentin-1, a novel adipokine expressed in visceral adipose tissue, is negatively correlated with insulin resistance and obesity. Decreased omentin-1 expression has been found in many chronic inflammatory diseases. However, the role of omentin-1 in coronary artery disease (CAD) has not been elucidated. The aim of the present study was to determine whether serum concentration of omentin-1 was independently associated with CAD.

Methods:

One hundred and fifty five patients with CAD were divided into two groups: acute coronary syndrome (ACS) and stable angina pectoris (SAP). A total of 52 healthy participants served as controls. Serum concentrations of omentin-1 and interleukin-6 (IL-6) were measured using ELISA. The association of omentin-1 with CAD and cardiovascular disease risk factors was evaluated.

Results:

Serum omentin-1 levels were lower in patients with ACS or SAP compared with controls (ACS, 113.08±61.43 ng/mL; SAP, 155.41±66.89 ng/mL; control, 254.00±72.9 ng/mL; P<0.01). Patients with ACS also had lower serum concentrations of omentin-1 compared with patients with SAP (P<0.01). Serum concentration of omentin-1 was negatively correlated with body mass index (r=−0.17, P<0.05) and serum IL-6 concentration (r=−0.19, P<0.05). Furthermore, multiple logistic regression analysis showed that serum omentin-1 concentrations were independently correlated with CAD.

Conclusion:

The findings suggest that serum concentrations of omentin-1 are related to CAD.