Pharmacists Increasingly Take on Clinical Roles

Anna Gorman

February 12, 2014

NORTHRIDGE, Calif. -- Jill Freedman felt like her heart was jumping out of her chest. She knew her blood pressure was too high and feared having a heart attack or a stroke.

"I was freaking out," said Freedman, 55. "You get very emotional when you think you could drop dead at any moment."

Her doctor doubled one of her medications, she said, but that only made her feel worse. So Freedman turned to the one person she knew she could count on -- her pharmacist.

"It was Diana who figured out what the problem was," said Freedman, referring to her longtime pharmacist Diana Arouchanova. "Had she not been on top of what I’m going through, God knows how many more weeks this could have potentially gone on."

Arouchanova, who owns Clinicare Pharmacy, reviewed Freedman's medications and realized that her problem stemmed from the dangerous combination of two prescriptions. She got the physician to change the medications and started checking Freedman's blood pressure daily. Soon, it began to drop.

Once limited to filling and dispensing drugs, pharmacists are increasingly providing direct care to patients. Across the country, they are working with doctors to give immunizations and help patients safely manage medications. In some places, they can even write prescriptions after a physician's diagnosis.

Jill Freedman, 55, visits her local pharmacist in Northridge, Calif., twice a week for a routine blood pressure check (Photo by Heidi de Marco/KHN).

California is among the states to give pharmacists the greatest flexibility, thanks in part to a law that took effect this year. Other states, including New Mexico and North Carolina, have also allowed pharmacists to take on more clinical responsibilities.

It's all part of a push by druggists and pharmacies to take a greater role in guiding patients and promoting good health. One prominent example is CVS Caremark's recent announcement that it will stop selling tobacco products to help customers become healthier.

At the same time, health officials are looking for ways to ease the strain on overloaded doctors, improve care and contain costs. With millions of people gaining coverage under the nation's health law, experts say pharmacists can fill gaps in primary care and help avoid unnecessary hospital admissions.

Pharmacists, who are required to have a doctorate in pharmacy, say technicians can fill prescriptions and that their training and education can be put to better use.

"We are the most overeducated and underutilized healthcare professional in the U.S.," said R. Pete Vanderveen, dean of the USC School of Pharmacy. "It doesn't take eight years of education and a professional doctorate to fill a bottle with pills."

The new California law designates pharmacists as health care providers and allows them to give routine vaccinations and provide some travel and birth-control medications. The law also creates a new class of provider known as an "advanced practice pharmacist." With additional training and experience, such as a residency program, advanced practice pharmacists will be able to collaborate with doctors in assessing and referring patients, starting and stopping medications and managing patients' diseases.

Some physicians, however, are wary of pharmacists doing too much on their own. The American Medical Association supports physician-led teams that include pharmacists, but opposes giving pharmacists prescription privileges without a doctor's supervision. The California Medical Association initially opposed the state law but withdrew the opposition after amendments were added, including one that limited the type of medications they could provide.

Pharmacist organizations are quick to point out they don't want to take over the physician's job.

"We are not looking to become the primary care provider for all patients," said Stacie Maass, a senior vice president at the American Pharmacists Association. "We want to be part of the team."

Diana Arouchanova, head pharmacist at Clinicare Pharmacy in Northridge, Calif., works with doctors to ensure patients take their medications and avoid unnecessary hospital admissions (Photo by Heidi de Marco/KHN).

Research has shown that pairing pharmacists and physicians can save money and improve health outcomes. Other studies are under way.

Clinical pharmacist Michelle Lee is funded by a federal grant to the USC School of Pharmacy and AltaMed Health Services to determine whether pharmacists can help high-risk patients control chronic diseases take their medications as prescribed and avoid hospitalization.

On a recent day at an AltaMed clinic in Boyle Heights, Calif., Lee stopped the medications of a liver disease patient whose condition might have worsened if he took what a local hospital just prescribed him. Then she ordered another check of his liver.

Lee also saw 57-year-old Maria Flores, who has uncontrolled diabetes, noticing that both her blood sugar and her blood pressure were higher than normal.

"Have you been under any stress?" Lee asked through a Spanish-language translator.

The woman started to tear up. She responded that there had been a death in the family and that she hadn't been able to sleep or eat. Lee ordered a shot of insulin and adjusted her blood-pressure medication. She reminded Flores to check her blood sugar every day.

"It's important for us to know if the insulin is at a good dose," she said. "We might need to make adjustments." 

As a student, Lee worked at Walgreens and customers frequently came in with questions. Lee said she wanted to do more for them. Now, Lee said she believes she is doing that. 

"It's a little role but I think it's making a big difference," she said.

Freedman appreciates the difference. She discovered Clinicare Pharmacy about seven years ago. In contrast to the chain drug store she'd been using, which she felt was impersonal, Arouchanova and her staff regularly called to see how she was feeling and to check on any side effects.

Now Arouchanova, 36, helps her track the more than a dozen medications she takes for hypertension, Crohn’s disease and ulcerative colitis. 

Clinical pharmacist Diana Arouchanova worked with patient Diana Freedman’s physician to switch one of the medications that helped lower her blood pressure (Photo by Heidi de Marco/KHN).

Freedman stops by a couple times a week, sometimes just to say hello. She considers her pharmacist a friend and brings her birthday presents. "I can walk in here any time of the day," she said. "There is somebody who greets me with a smile."

Arouchanova, an Armenian immigrant with a bob of short blond hair, said she tries to go "above and beyond the call of duty."

"I take care of each of my patients as if they were my only patients," she said. That means working up to 12 hours a day and only seeing her young son briefly in the morning and evening.

One day a week, a physician, Hanriet Minasian, works out of an office in the pharmacy. She and Minasian have an agreement that allows Arouchanova to order labs and to start, stop and adjust medications. They refer patients to one another and together review their patients' charts.

Erika Pappas, 34, who lives in nearby Reseda, sees both Arouchanova and Minasian for her diabetes and hypertension.

"I don't have to worry about my pharmacist or my doctor not being on the same page," she said during a recent visit. "Everything is very clear."

Minasian said Arouchanova is another set of eyes on complex cases -- patients with multiple chronic diseases who receive numerous prescriptions. 

"It's like a checks and balances system," Minasian said. "The more heads you put together, the better care we can provide for our patients."

Fracture Risk Increased With Use of Certain Diabetes Drugs

News Author: Miriam E. Tucker
CME Author: Laurie Barclay, MD

 Faculty and Disclosures

CME/CE Released: 08/07/2014 ; Valid for credit through 08/07/201

CLINICAL CONTEXT

By reduction of bone mineral density, adipocyte stimulation, and inhibition of osteoclast differentiation, thiazolidinediones (TZDs) may increase the risk for fractures. Previous research has suggested that fracture risk is increased in patients treated for diabetes with TZDs compared with those treated with metformin.

However, previous epidemiologic research has not shown an increased fracture risk with sulfonylureas. The goal of this observational study, results which were presented at the American Diabetes Association 2014 Scientific Sessions, was to compare fracture risk among multiple classes of glucose-lowering agents.

STUDY SYNOPSIS AND PERSPECTIVE

The oral diabetes drug classes of TZDs and sulfonylureas both boost the risk for fractures compared with metformin, a large database analysis has found.

The observational study confirms previous findings of increased fracture risk with TZDs but is the first to compare multiple classes of glucose-lowering agents and the first to suggest a possible increased fracture risk for sulfonylureas, Sandhya Mehta, PhD, an investigator with a technology company specializing in large data analytics, told the American Diabetes Association 2014 Scientific Sessions.

Dr. Mehta said her study findings should be taken into consideration in prescribing antidiabetic drugs, especially in those patients already at higher risk for fracture.

"Be more careful with TZDs, to be sure, and also with sulfonylureas," she told Medscape Medical News, but she added that the association with sulfonylureas needs confirmation.

Indeed, session moderator Amanda I. Adler, MD, PhD, from Addenbrooke's Hospital, Cambridge University, United Kingdom, and chair of the Technology Appraisal Committee of the United Kingdom's National Institute for Health and Care Excellence, told Medscape Medical News that despite the investigators' attempts to control for many potential confounders, "One concern is residual confounding, that patients who take sulfonylureas are at higher risk for fractures than those who don't take sulfonylureas."

More Work Needed to Drill Down Into Sulfonylurea Fracture Risk

Dr. Mehta and colleagues retrospectively analyzed 2008-2012 data from the Medical Outcomes for Effectiveness and Economics registry of more than 100 million individuals. A total of 99,892 adults were identified as new users of glucose-lowering drugs: metformin (77.8%), sulfonylureas (15.3%), dipeptidyl peptidase-4 (DPP-4) inhibitors (2.7%), TZDs (2.7%), incretins (0.81%), and meglitinides (0.6%).

Within the 5-year follow-up period, 7353 patients (7.4%) had evidence of fracture.

The incidence of fractures was 6.8% among the total 76,924 patients taking metformin, 10.9% among the 2679 taking TZDs, and 9.7% in the 15,162 receiving sulfonylureas. Rates for other glucose-lowering agents ranged from 6.1% of 799 individuals taking incretin drugs to 10.7% of the 626 receiving meglitinide.

After adjustment for age, gender, region, a variety of medical conditions, and other medications, the hazard ratios (HRs) for fracture risk compared with metformin were 1.40 for TZDs (P < .0001) and 1.09 for sulfonylureas (P = .0054). The increase in fracture risk for the other drug classes compared with metformin did not reach statistical significance.

In her presentation, Dr. Mehta noted that the findings support the hypothesis that TZDs increase fracture risk by decreasing bone mineral density, stimulating adipocytes, and inhibiting osteoclast differentiation.

She noted, however, that previous epidemiologic studies have not found an increased fracture risk with sulfonylureas. "The present study points to the need of further investigation on the association between sulfonylureas and the risk of fractures."

Dr. Adler told Medscape Medical News that what preceded the fracture is important information. "If they were having more low blood sugars and consequently fell, it would be interesting to know, but unfortunately she couldn't tell us."

She also noted that although the findings for the other glucose-lowering drugs are reassuring, "[w]e can't really know what they're doing to bones without knowing what else is going on. If you took a drug that made you more likely to topple over, your bones could be equally as strong as the group that didn't fall over, but [you could] still have more fractures."

Dr. Mehta and Dr. Adler have disclosed no relevant financial relationships.

American Diabetes Association 2014 Scientific Sessions; June 15, 2014. 165-OR

STUDY HIGHLIGHTS

• The investigators used a large administrative claims database for this longitudinal, retrospective cohort study.
• Using multivariate survival analysis, they assessed the comparative safety regarding fracture risk for antidiabetic agents including sulfonylureas, biguanides (metformin), incretin mimetic agents, meglitinide analogues, TZDs, and DPP-4 inhibitors.
• Inclusion criteria for the cohort were age 18 years or older, newly prescribed only a single class of antidiabetic agents, diagnosed with diabetes before starting treatment, continuously enrolled for 12 months before and at least 12 months after starting treatment, and not diagnosed with fracture in the 12 months preceding treatment.
• Patient data were censored at the time of fracture, when they left the cohort, or at the end of the follow-up period.
• Of 99,892 new adult users of antidiabetic drugs, 77.8% were receiving metformin, 15.3% were receiving sulfonylureas, 2.7% were receiving DPP-4 inhibitors, 2.7% were receiving TZDs, 0.81% were receiving incretins, and 0.6% were receiving meglitinides.
• During the 5-year follow-up, fracture occurred in 7353 patients (7.4%).
• Compared with metformin use, sulfonylurea use and TZD use were associated with significantly higher fracture risk.
• The HR was 1.09 for sulfonylureas (95% confidence interval [CI], 1.03 - 1.16; P = .0054) and 1.40 for TZDs (95% CI, 1.25 - 1.58; P < .0001), after adjustment for potential confounders including age, gender, region, medical comorbidities, and use of other medications.
• Fracture risk with metformin was not statistically significantly different from that seen with other classes of antidiabetic agents. Fracture rates ranged from 6.1% of 799 patients taking incretin drugs to 10.7% of 626 patients taking meglitinide.
• On the basis of the findings of their large longitudinal study, the investigators conclude that fracture risk is 9% to 40% greater in users of sulfonylureas and TZDs.
• The authors recommend that clinicians consider these findings when prescribing antidiabetic drugs, especially for those patients already at greater risk for fracture.
• Limitations of this study include its observational design with the potential for residual confounding factors, in that patients who take sulfonylureas may be at greater risk for fractures than those who do not take these drugs.

CLINICAL IMPLICATIONS

• Findings of a large, longitudinal, retrospective cohort study suggest that fracture risk is 40% greater in users of TZDs than in users of metformin. Clinicians should consider these findings when prescribing antidiabetic drugs, particularly for patients who are already at increased fracture risk.
• This study also suggests that fracture risk is 9% greater in users of sulfonylureas than in users of metformin.

Pharmacoepidemiology of common colds and upper respiratory tract infections in children and adolescents in Germany

Nathalie Eckel¹, Giselle Sarganas², Ingrid-Katharina Wolf² and Hildtraud Knopf^2*

• *Corresponding author: Hildtraud Knopf knopfh@rki.de

Author Affiliations

¹German Institute of Human Nutrition Potsdam-Rehbrücke, Department of Molecular Epidemiology, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Potsdam, Germany

²Robert Koch-Institute, Department of Epidemiology and Health Monitoring, General-Pape-Str. 62-66 12101, Berlin, Germany

BMC Pharmacology and Toxicology 2014, 15:44  doi:10.1186/2050-6511-15-44

Received:	12 December 2013
Accepted:	6 August 2014
Published:	9 August 2014

© 2014 Eckel et al.; licensee BioMed Central Ltd. 

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Abstract

Background

Medicines to treat common colds (CC) and upper respiratory tract infections (URTI) are widely used among children, but there are only few data about treatments actually applied for these diseases. In the present study we analyze the prevalence and correlations of self-medicated and prescribed drug use for the treatment of CCs and URTIs among children and adolescents in Germany.

Methods

Medicine use during the week preceding the interview was recorded among 17,450 children (0–17 years) who participated in the drug interview of the 2003–2006 German Health Interview and Examination Survey for Children and Adolescents (KiGGS). The definition of CCs and URTIs in the present study included the WHO-ICD-10 codes J00, J01.0, J01.9, J02.0, J02.9, J03.0, J03.9, J04.0, J06.8, J06.9, J11.1, J11.8, R05 and R07.0. Using the complex sample method, the prevalence and associated socio-demographic factors of self-medication, prescribed medicines and antibiotics were defined.

Results

13.8% of the participating girls and boys use drugs to treat a CC or an URTI. About 50% of this group use prescribed medications. Among the users of prescribed medication, 11.5% use antibiotics for the treatment of these diseases. Looking at all prescribed medicines we find associations with younger age, immigration background, and lower social status. Antibiotic use in particular is associated with female sex, higher age, residency in the former East Germany and immigration background.

Conclusions

The use of medicines to treat CCs or URTIs is widespread among children and adolescents in Germany. Thus, longitudinal studies should investigate the risks associated with this drug use. Differences in socio-demographic variables regarding exposure to antibiotic use indicate that there could be an implausible prescribing behavior among physicians in Germany.

Keywords: 

Common cold; Upper respiratory tract infection; Cough & cold medicines; Pharmacotherapy; Antibiotics; Children; KiGGS

Background

Common colds (CCs) and other upper respiratory tract infections (URTIs) are usually self-limiting conditions with a high prevalence worldwide. Earlier analyses of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) indicate that the 1-year-average-prevalence of CCs among children and adolescents amounts to 88.5%, with the highest prevalence among children aged 3 to 6 years - almost 94% [1]. According to the literature, an average child undergoes a minimum of 4 to 8 URTIs per year [2-4]. Due to missing or low immunity in the first years of life, children are particularly vulnerable to viral infections [5].

Medicines against CCs and its symptoms are widely marketed, e.g. cough medicines, nasal decongestants, throat medicines, but also vitamins and herbal or homeopathic medicines. Data of the statutory health insurance document that 9 of the 20 most often prescribed drugs for children and adolescents belong to cough&cold medicines (CCMs) [6]. Additionally, many of these drugs are acquired over-the-counter (OTC) [7]. Analyzing children’s and adolescents’ use of medications to treat CCs and URTIs throws light on the prevalence and related factors of drug use and is an essential step for understanding issues concerning their safety. Data from health insurances and sales figures are not able to completely provide this transparency as they do not necessarily correspond to the actual medication usage. In the USA, serious adverse events and even some deaths are associated with the use of OTC CCMs [8,9]. About 7% of all pediatric prescriptions for the respiratory tract system are not officially licensed for use in children, which means that they have never been tested rigorously for pediatric safety and efficacy [10]. Earlier analyses of KiGGS suggest that about 30% of the medicines are used off-label in terms of under-dosing, over-dosing, untested indication, or age [11].

Antibiotics are usually not indicated for viral infections such as uncomplicated URTIs or CCs. Antibiotics do not lead to an improvement of CC and URTI symptoms, but they yield potential side effects [12,13]. Nevertheless, their use is common: Data from the statutory health insurance show that an URTI is the main reason for an antibiotic prescription. The data also indicate that antibiotic use is highest among children aged 0 to 4 years [14]. High and unnecessary antibiotic consumption is not only a problem for the individual but for the whole population, as this is one of the main reasons for antibiotic resistances [15].

However, national representative data regarding the pharmacoepidemiology of CCs and URTIs in the child population of Germany are lacking. By analyzing data of the KiGGS survey we attempt to fill this knowledge gap. We describe prevalence rates, investigate socio-demographic characteristics and analyze factors associated with the use of CC and URTI medicines. The analyses are differentiated into the use of overall CCMs, prescribed CCMs, self-medicated CCMs, and antibiotic use.

Methods

KiGGS, a nationwide representative Health Interview and Examination Survey for children and adolescents, was conducted by the Robert Koch Institute between May 2003 and May 2006. The target population comprised all non-institutionalized residents of Germany between 0 and 17 years of age. Therefore, children and adolescents with a foreign nationality were also included. A detailed description of the methods of KiGGS have been published elsewhere [16]. Briefly, two-stage sampling procedures were applied. In the first stage 167 municipalities were drawn. This sample was representative for municipality sizes and structures in Germany. In the second stage, samples of children and adolescents aged between 0 and 17 years were drawn randomly from the corresponding local population registries. In total, 17,641 participants were included in the survey which equated to a response rate of 66.6%. Nonresponse analysis showed only little differences in socio-demographic and health-related variables between responders and non-responders. The survey was approved by the Ethics Committee of the Virchow Hospital, Humboldt University Berlin and federal data-protection officials. The children’s parents/guardians and/or children aged 14 years or older were informed about all aspects of the survey and they submitted a written consent [17].

Standardized, age-specified self-administered questionnaires filled out by parents/guardians and children aged 11 years or older were used to collect socio-demographic data, family background and health-related issues. The children’s age was categorized in 5 age groups: 0–2, 3–6, 7–10, 11–13, and 14–17 years. Children with immigration background were defined as those who had no German nationality themselves or whose parents had no German nationality. In order to calculate the socio-economic status according to Winkler, the parents’ education, professional classification and household net income were inquired [16]. Medicine use was investigated in a standardized computer-assisted face-to-face-interview by a physician. Information on medicine use was collected by asking the parents and the children themselves. The participants were asked to bring all of the original packages of medicines used in the last 7 days to the interview. Drug use was assessed by the following question: “Has your child taken any medicines in the last 7 days? Please also mention any ointments, lineaments, contraceptive pills, vitamin and mineral supplements, medicinal teas, herbal medicines and homeopathic medicines.” For all of the used drugs further information was collected, such as the form of administration, frequency of intake, origin (‘prescribed by a doctor’, ‘prescribed by a non-medical practitioner’, ‘bought over the counter’, ‘obtained from other sources’), duration of use, improvement of the condition(s) treated, and degree of tolerability. In addition, up to two conditions for which the medication was taken were registered. The reported medicines were classified according to the Anatomical Therapeutic Chemical (ATC) codes and the conditions treated according to the WHO International Classification of Diseases-10 codes (WHO ICD-10 codes) [18]. To evaluate the medication used for CCs or URTIs we included the following conditions (WHO-ICD-10 codes in brackets): CC (J00), acute sinusitis (J01.0, J01.9), acute pharyngitis (J02.0, J02.9), acute tonsillitis (J03.0, J03.9), acute laryngitis (J04.0), acute respiratory tract infections (J06.8, J06.9), influenza (J11.1, J11.8), cough (R05) and sore throat (R07.0).

All statistical analyses were performed using SPSS statistical software 18.0. The analyses were performed with a weighting factor to adjust for deviations in demographic characteristics (age, sex, residence in West or former East Germany, level of urbanity) in comparison to the national child population. Descriptive statistics were used to estimate the prevalence of medication use to treat CCs or URTIs according to sex, age, region of residence, immigration background, and social status. Prevalence of self-medication, prescribed medicines and antibiotic use were estimated among those children who used drugs to treat CCs or URTIs. Odds Ratios (ORs) were obtained from multivariate logistic regression models to depict associations between socio-demographic factors and self-medication, use of prescribed medicines and antibiotic use. Results with a probability level of p < 0.05 and 95% confidence intervals (CIs) not including the value 1 were considered as statistically significant.

Results

Characteristics of the study population stratified by gender are listed in Table  1. 16.5% of all participants are living in the former East Germany and about 17% have an immigration background. The largest part of the boys and girls come from families with an intermediate social status. No significant differences are observed between girls and boys regarding the listed socio-demographic characteristics.2,595 children and adolescents used 3,648 medicines to treat a CC or URTI during the last 7 days. The vast majority of these medicines are drugs acting on the respiratory system (ATC code R00, 84.0%), followed by homeopathic medicines (Z00, 5.0%) and anti-infectives for systemic use (J00, 4.7%). 21% of the used medicines are not recorded on the last 5th level of the ATC-codes (level of the chemical substance), because participants forgot the brand names. Therefore, only 2,887 medicines could get analyzed on the basis of their active ingredients. The 10 most frequently used active ingredients are shown in Figure  1.

Table 1. Socio-demographic characteristics of survey participants by gender

Figure 1. The 10 most frequently used active ingredients to treat common colds (CCs) or upper respiratory tract infections (URTIs). German Health Interview and Examination Survey for Children and Adolescents (KiGGS), 2003-2006.

Table  2 illustrates the prevalence rates of drug use to treat CCs or URTIs during the last 7 days. 14.3% (95% CI 13.2%, 15.5%) of the study participants use medicines to treat a CC or an URTI. The use of those medicines decreases with rising age. All other socio-demographic variables (region, immigration background and social status) show no statistically significant differences. About half of the children using drugs to treat CCs or URTIs, utilize drugs prescribed by a physician (Table  2). The proportion decreases with rising age. Furthermore, we observed a statistically significant association between the use of prescribed medicine and immigration background as well as lower socio-economic status. The proportion of using self-medication to treat CCs and URTIs amounts to 57.6%. This proportion increases with higher age and is also higher for children without migration background and for children from families with a high social status (Table  2). Among those children and adolescents who use prescribed drugs, the antibiotic use is 11.6% (95% CI 9.8%, 13.7%). The antibiotic use in the descriptive analysis is significantly associated with immigration background and older age.

Table 2. Prevalence rates, proportions of overall prescribed medicines, proportion of self-medication and proportion of prescribed antibiotics to treat common colds (CCs) or upper respiratory tract infections (URTIs) (n = 17,450)

Multivariate logistic regression models show that the use of self-medication is significantly associated with higher age (OR 2.40; 95% CI 1.87, 3.07), no immigration background (OR 1.64; 95% CI 1.28, 2.11) and high (OR 1.77; 95% CI 1.42, 2.20) or intermediate (OR 1.44; 95% CI 1.16, 1.82) social status. In contrast, use of prescribed medicines is significantly associated with immigration background (OR 1.60; 95% CI 1.21, 2.11), younger age (OR 2.27; 95% CI 1.81, 2.85) and lower socio-economic status (OR 1.58; 95% CI 1.25, 1.99). Antibiotic use is significantly associated with immigration background (OR 2.37; 95% CI 1.51, 3.73), female gender (OR 1.52, 95% CI 1.05, 2.18), older age (OR 1.45; 95% CI 1.01, 2.08) and residency in former East Germany (OR 1.67; 95% CI 1.19, 2.34) (Table  3).

Table 3. Socio-economic characteristics associated with the use of self-medication, prescribed medicine and antibiotics to treat common colds (CCs) and upper respiratory tract infections (URTIs) (n = 17,450)

Discussion

The present study documents a high prevalence of medicine use to treat CCs or URTIs among children and adolescents in Germany. About 14% of the boys and girls use at least one of these medicines within a given week. The most frequently used medicines are drugs acting on the respiratory system followed by homeopathic medicines and anti-infectives for systemic use. About half of the children with medicine use to treat CCs and URTIs use prescribed medicine. Almost 60% of children with CCMs use self-medication. Self-medication is associated with higher age, no immigration background, and high or intermediate social-status. In contrast, children of younger age, with an immigration background, and from families with low social-status use significantly more often prescribed drugs. Furthermore, antibiotic use is significantly associated with higher age, female sex, immigration background, and residency in former East Germany.

Data of medicine use based on treated conditions are sparse worldwide. The Slone Survey (1999–2006), a representative random-digit-dialing survey collecting data on medication use among the USA population during the last 7 days, observes a prevalence of children’ s exposure to CCMs of 10.1%. The definition CCMs includes all oral medications containing ≥ 1 antitussive, decongestant, expectorant or first-generation-antihistamine [19]. In KiGGS, expectorants are more frequently used than antitussives (6.7 vs. 1%), whereas in the Slone Survey, antitussives are more often used than expectorants (4.1 vs. 1.5%). Furthermore, there are differences regarding the active ingredients for certain medications, such as in antitussives and expectorants. The Slone Survey shows a high usage of dextromethorphan in antitussives and guafenisin in expectorants, whereas in our study, the most frequent active ingredients in expectorants are ambroxol, ivy leafs and acetylcystein and the most often used active ingredient in antitussives is clobutinol. The use of clobutinol has ceased since the year 2007 when all medicines containing clobutinol were withdrawn from the market. Data from a cohort study in South-West England, which were collected by self-administered questionnaires, yield exposure prevalences of 43.1% to CCMs, 5.0% to rhinologicals and 4.3% to throat medicines in the last 12 months among children aged up to 7.5 years [20]. However, comparability of these results with our prevalence rates (8.9% for CCMs, 5.9% for rhinologicals, 1.0% for throat medicines) is limited, mainly because of the difference in the reference periods. Longer observation periods lead to higher prevalence rates but also increase susceptibility for recall-bias. Despite of a much shorter observation period in our survey, the prevalence rate of rhinological use is higher in our study. This implies the probability of a higher 12 month prevalence in Germany compared to South-West England.

In our study self-medication for treating URTI is more common among children with higher age and among those without immigration background. These findings correspond to earlier analyses of KiGGS data looking at overall self-medication [7]. Moreover, our results suggest that self-medication is associated with a higher social-status. The same results are reported by a study looking at overall self-medication in Dutch adolescents [21]. In contrast to self-medication, the prevalence of using prescribed medicine is decreasing with higher age in our study, which is in accordance with results of the SLONE survey and a cohort study in three European countries[19,22]. Furthermore, in the present study the use of prescribed medication to treat CCs and URTIs is strongly associated with having an immigration background and a lower social-status. This finding is partly in line with earlier studies. A study in Poland observes positive associations between physician consultations and low school-leaving qualifications, as well as between use of OTC medicines and a high household income when treating respiratory tract infections in adults[23]. An Israeli cross-sectional study analyzes reasons why patients with flu-like symptoms consult a doctor. The reason “to get a prescription” is associated with low school-leaving qualifications, low income and unemployment [24]. However, Dutch secondary data analysis observes no association between use of prescription medicines and social-status by adolescents for all conditions [21].

Earlier findings looking at prevalence rates for antibiotic use among children in Europe and in the USA range from 31% to 38% [25-27]. However, these data refer to patients who were visiting a physician, thus comparability to our findings is limited. Our results suggest an increasing antibiotic use with higher age and with female sex. A previous study based on KiGGS data shows that children of younger age are more often exposed to antibiotic use compared to older children [28]. However, this study analyses the overall antibiotic use while the present study only looks at antibiotic use for treatment of CCs and URTIs. Our findings are probably influenced by not having included otitis media in the definition of URTIs, as the prevalence of otitis media is strongly decreasing with higher age [1]. Health insurance data on antibiotic use in Germany does not differentiate according to age or indication [14]. Gender differences concerning antibiotic use are already known: Data from the National Ambulatory Medical Care Survey from 1992 in the USA indicate a significant positive association between antibiotic consumption and female sex [29]. Moreover, findings from Abbas et al. suggest higher antibiotic use for girls compared to boys in all age groups except for 2-4-years old children [30]. Our results regarding regional differences are in line with the results of the EVA survey (Einflüsse auf die ärztliche Verschreibung von Antibiotika in Deutschland) which investigates influences on prescribing patterns by physicians in Germany. This survey demonstrates that physicians in the eastern part of Germany prescribe antibiotics more frequently than in the western part [31]. Moreover, our results suggest an association between antibiotic use for CCs and URTIs and children with immigration background. The findings of earlier studies investigating this association are inconsistent. Neither a Swedish prospective cohort study nor a Norwegian survey observes an association between antibiotic consumption and immigration background [32,33]. A Cyprian cross-sectional-study finds a higher inappropriate antibiotic use by children with immigration background [34]. Furthermore, data of an Italian cohort-study suggests a significant higher antibiotic prescribing rate for URTIs for children with immigration background[27]. Altiner et al. report as a result of a qualitative study that physicians often tend to misinterpret the patients’ demands and often feel urged by the patients to give them an antibiotic prescription. This pressure is especially felt in consultations with Turkish immigrants [35,36].

A major strength of our study is the large number of population-representative data with a high response-rate including non-responder-analyses and quality assurances measures. The parents or the adolescents themselves were asked to bring the packages of the medicines used in the previous week to the interview. In contrast to health-insurance data, we analyze the medication actually used by children and adolescents, not only prescribed and potentially never used medicines. However, our study has some limitations. Although the personal interview was conducted by a physician, indications were only reported by the parents or adolescents and were not validated. Because of language difficulties and possible cultural differences in symptom reporting, this might result in more imprecisely measured data particularly among children with immigration background. Recall bias has to be considered which would result in underreporting. By limiting the observation period to 7 days prior to the interview we tried to minimize recall bias. Because of the cross-sectional design of the survey it is not possible to draw conclusions on the risks children and adolescents are to exposed to the used medicines. A longitudinal study is required to examine this. Furthermore, although all reported conditions were documented and confirmed by medical professionals, a standardized severity assessment was not carried out. Thus, we are not able to asses if the antibiotic prescribing was unnecessary.

Conclusions

In summary, our study shows that the medicine use to treat CCs or URTIs is highly prevalent among children in Germany. Thus, longitudinal studies should investigate potential risks concerning this drug use. Furthermore, differences in socio-demographic variables, particularly sex, age, immigration background, and the difference between West and former East Germany, regarding antibiotic use indicate that there could be an implausible prescribing behavior among physicians in Germany. Thus, physicians should get trained to follow established guidelines when prescribing antibiotics for CCs and URTIs.

References

1. Kamtsiuris P, Atzpodien K, Ellert U, Schlack R, Schlaud M: [Prevalence of somatic diseases in German children and adolescents. Results of the German health interview and examination survey for children and adolescents (KiGGS)].
   Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2007, 50:686-700. 
2. Padberg J, Bauer T: [Common cold].
   Dtsch Med Wochenschr 2006, 131:2341-2349. 
3. Stickler GB, Smith TF, Broughton DD: Review: the common cold.
   Eur J Pediatr 1985, 144:4-8. 
4. Lorber B: Perspectives: the common cold.
   J Gen Intern Med 1996, 11:229-236. 
5. Gebel J, Teichert-Barthel U, Hornbach-Beckers S, Vogt A, Kehr B, Littmann M, Kupfernagel F, Ilschner C, Simon A, Exner M: [Hygiene tips for kids. Concept and examples of realisation].
   Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2008, 51:1304-1313. 
6. Jahnsen K: Arzneimitteltherapie im Kindes- und Jugendalter [in German].
   GEK-Arzneimittelreport 2008, 61:98-111. 
7. Du Y, Knopf H: Self-medication among children and adolescents in Germany: results of the National Health Survey for Children and Adolescents (KiGGS).
   Br J Clin Pharmacol 2009, 68:599-608. 
8. Rimsza ME, Newberry S: Unexpected infant deaths associated with use of cough and cold medications.
   Pediatrics 2008, 122:318-322. 
9. Schaefer MK, Shehab N, Cohen AL, Budnitz DS: Adverse events from cough and cold medications in children.
   Pediatrics 2008, 121:783-787. 
10. Bücheler R, Meisner C, Kalchthaler B, Mohr H, Schröder H, Mörike K, Schwoerer P, Schwab M, Gleiter CH: “Off-label”Verschreibung von Arzneimitteln in der ambulanten Versorgung von Kindern und Jugendlichen [in German].
    Dtsch Med Wochenschr 2002, 127:2551-2557. 
11. Knopf H, Wolf IK, Sarganas G, Zhuang W, Rascher W, Neubert A: Off-label medicine use in children and adolescents: results of a population-based study in Germany.
    BMC Public Health 2013, 13:631. 
12. Arroll B, Kenealy T, Falloon K: Are antibiotics indicated as an initial treatment for patients with acute upper respiratory infections? A review.
    NZJM 2008, 121:63-70. 
13. Fahey T, Stocks N, Thomas T: Systematic review of the treatment of upper respiratory tract infection.
    Arch Dis Child 1998, 79:225-230. 
14. Kern WV: Antibiotika und Chemotherapeutika [in German]. In Arzneiverordnungs-Report 2007: Aktuelle Daten, Kosten, Trends und Kommentare. Edited by Schwabe U, Paffrath D. Berlin Heidelberg NewYork Tokyo: Springer Verlag; 2008:287-311. 
15. Schröder H, Nink K, Günther J, Kern WV: Antibiotika: Solange sie noch wirken… [in German].
    GGW 2003, 3:7-16. 
16. Kurth BM, Bergmann KE, Hölling H: The National child and adolescent health survey. The complete concept.
    Gesundheitswesen 2002, 64(Suppl 1):3-11. 
17. Kamtsiuris P, Lange M, Schaffrath Rosario A: [The German health interview and examination survey for children and adolescents (KiGGS): sample design, response and nonresponse analysis].
    Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2007, 50:547-556. 
18. Knopf H: [Medicine use in children and adolescents. Data collection and first results of the German health interview and examination survey for children and adolescents (KiGGS)].
    Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2007, 50:863-870. 
19. Vernacchio L, Kelly JP, Kaufman DW, Mitchell AA: Medication use among children <12 age="" from="" in="" nbsp="" of="" results="" slone="" states:="" strong="" survey.="" the="" united="" years="">
    Pediatrics 2009, 124:446-454. 
20. Headley J, Northstone K: Medication administered to children from 0 to 7.5 years in the Avon longitudinal study of parents and children (ALSPAC).
    Eur J Clin Pharmacol 2007, 63:189-195. 
21. Tobi H, Meijer WM, Tuinstra T, de Jong-van den Berg LT: Socio-economic differences in prescription and OTC drug use in Dutch adolescents.
    Pharm World Sci 2003, 25:203-206. 
22. Sturkenboom MCJM, Verhamme KMC, Nicolosi A, Murray ML, Neubert A, Caudri D, Picelli G, Sen EF, Giaquinto C, Cantarutti L, Baiardi P, Felisi MG, Ceci A, Wong ICK: Drug use in children: cohort study in three European countries.
    BMJ 2008, 337:2245-2245. 
23. Baran S, Teul I, Ignys-O’Byrne A: Use of over-the-counter medications in prevention and treatment of upper respiratory tract infections.
    J Physiol Pharmacol 2008, 59:135-143. 
24. Kahan E, Giveon SM, Zalevsky S, Imber-Shachar Z, Kitai E: Behavior of patients with flu-like symptoms: consultation with physician versus self-treatment.
    IMAJ 2008, 2:421-425. 
25. Nash DR, Harman J, Wald ER, Kelleher KJ: Antibiotic prescribing by primary care physicians for children with upper respiratory tract infections.
    Arch Pediatr Adolesc Med 2002, 156:1114-1119. 
26. Meropol SB, Chen Z, Metlay JP: Reduced antibiotic prescribing for acute respiratory infections in adults and children.
    Br J Gen Pract 2009, 59:e321-e328. 
27. Moro ML, Marchi M, Gagliotti C, Di Mario S, Resi D, Progetto Bambini a Antibiotici [ProBA]” Regional Group: Why do paediatricians prescribe antibiotics? Results of an Italian regional project.
    BMC PEdiatr 2009, 9:69. 
28. Robert Koch-Institut, Bundeszentrale für gesundheitliche Aufklärung: Erkennen – Bewerten – Handeln: Zur Gesundheit von Kindern und Jugendlichen in Deutschland [in German]. Berlin: Robert Koch-Institut; 2008. 
29. Gonzales R, Steiner JF, Sande MA: Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians.
    JAMA 1997, 278:901-904. 
30. Abbas S, Ihle P, Heymans L, Kupper-Nybelen J, Schubert I: [Differences in antibiotic prescribing between general practitioners and pediatricians in Hessen, Germany].
    Dtsch Med Wochenschr 2010, 135:1792-1797. 
31. Velasco E, Eckmanns T, Espelage W, Barger A, Krause G: Einflüsse auf die ärztliche Verschreibung von Antibiotika in Deutschland (EVA-Studie): Abschlussbericht an das Bundesministerium für Gesundheit [in German]. Berlin: Robert Koch-Institut; 2009. [Report from the Department for Infectious Disease Epidemiology] 
32. Hedin K, Andre M, Hakansson A, Mölstad S: A population based study of different antibiotic prescribing in different areas.
    Br J Gen Pract 2006, 56:680-685. 
33. Soma M, Slapgård H, Lerberg M, Lindbaek M: [Patients’ expectations of antibiotics for acute respiratory tract infections].
    Tidsskr Nor Laegeforen 2005, 125:1994-1997. 
34. Rousounidis A, Papaevangelou V, Hadjipanayis A, Panagakou S, Theodoridou M, Syrogiannopoulos G, Hadjichristodoulou C: Descriptive study on parents’ knowledge, attitudes and practices on antibiotic use and misuse in children with upper respiratory tract infections in Cyprus.
    Int J Environ Res Public Health 2011, 8:3246-3262. 
35. Altiner A, Knauf A, Moebes J, Sielk M, Wilm S: Acute cough: a qualitative analysis of how GPs manage the consultation when patients explicitly or implicitly expect antibiotic prescriptions.
    Fam Pract 2004, 21:500-506. 
36. Sahlan S, Wollny A, Brockmann S, Fuchs A, Altiner A: Reducing unnecessary prescriptions of antibiotics for acute cough: adaptation of a leaflet aimed at Turkish immigrants in Germany.
    BMC Fam Pract 2008, 9:57