Henry Milgrom

Measurement of children's asthma medication adherence by self report, mother report, canister weight, and Doser CT

BACKGROUNDnAccurate assessment of medication adherence has been difficult to achieve but is essential to drug evaluation in clinical trials and improved outcomes in clinical care.nnnOBJECTIVEnThis study was conducted to compare four adherence assessment methods: child report, mother report, canister weight, and electronic measurements of metered dose inhaler (MDI) actuation.nnnMETHODSnParticipants included 27 children with mild-to-moderate asthma who were followed prospectively for 6 months. All patients used an MDI equipped with an electronic Doser attached to their inhaled steroid. At each 2-month follow-up visit, Doser and canister weight data were recorded, while child and mother were interviewed separately regarding medication use.nnnRESULTSnChildren and mothers reported, on average, over 80% adherence with the prescribed inhaled steroid. Canister weight revealed, on average, adherence of 69%, significantly lower than self-report. When adherence recorded by the electronic Doser was truncated to no more than 100% of prescribed daily use, average adherence was 50%. Older children and adolescents, nonwhite children, and those from poorer functioning families were least adherent.nnnCONCLUSIONSnElectronic adherence monitoring was significantly more accurate than self-report or canister weight measures. Such accuracy is an essential prerequisite to increasing understanding of the treatment, setting, and patient factors that influence adherence, and to the consequent design of effective intervention strategies.

Nonadherence in Asthmatic Patients: Is there a Solution to the Problem ?

LEARNING OBJECTIVESnReading this article will reinforce the readers awareness of the relationship between adherence and treatment outcome, of the causes of nonadherence, of methods of measurement, and of steps toward successful intervention.nnnDATA SOURCESnArticles on adherence to asthma therapy were reviewed. A MEDLINE database using subject keywords was searched from 1990 through 1997.nnnSTUDY SELECTIONnPertinent articles were chosen, with preferential presentation of results from controlled studies.nnnRESULTSnThere is no evidence of recent improvement in the rates of nonadherence, and patients continue on average to take about 50% of prescribed medication. Nonadherence assessment is most accurate when it can be measured objectively, and relies neither on patient report nor physician estimate. The consequences of nonadherence are measured in patient suffering, financial cost, and serious compromise of clinical trial outcomes. Underlying causes of nonadherence are traced to characteristics of the disease, treatment, patient, and caregiver system.nnnCONCLUSIONnImproved adherence will lead to improved disease control, but only if medical care systems encourage and support the allocation of sufficient resources to allow barriers to self-management to be discussed and solutions negotiated. Attempts to improve adherence outside of the caregiver-patient relationship are less likely to succeed. Special programs for difficult-to-manage patients are necessary to change behavior, although significant illness improvement and cost savings are likely to result.

Psychological factors associated with medication nonadherence in asthmatic children

Adherence with inhaled beta-agonists and corticosteroids in 24 asthmatic children was tracked over 3 months utilizing the metered-dose inhaler chronolog (MDIC). Patients seldom took all of their medications as prescribed, and failed to take any inhaled corticosteroid doses on a median of 41.8% of days or inhaled beta-agonists on 28.1% of days despite prescribed daily use. Medication nonadherence was correlated with lower levels of asthma knowledge (Asthma Knowledge Questionnaire) and family dysfunction (Family Assessment Device), but not child behavior disorder (Child Behavior Checklist). Patients tended to dramatically over-report medication use. Improved identification of the markers of nonadherence can directly facilitate more efficient targeting of behavioral interventions, resulting in improved adherence, better illness control, and less requirement of urgent medication intervention.

Comparison of ipratropium bromide 0.03% with beclomethasone dipropionate in the treatment of perennial rhinitis in children.

OBJECTIVEnTo compare the safety and efficacy of ipratropium bromide 0.03% (IB) with beclomethasone dipropionate 0.042% (BDP) in the treatment of perennial rhinitis in children.nnnMETHODSnThirty-three children with nonallergic perennial rhinitis (NAPR) and 113 with allergic perennial rhinitis (APR) were randomly assigned to either IB or BDP for 6 months in a single-blind, multicenter protocol in which the physician was blinded to treatment. At each visit, patients and physicians rated symptom control of rhinorrhea, nasal congestion, and sneezing. Patients also completed quality of life questionnaires at baseline and after 6 months of therapy.nnnRESULTSnBoth treatments showed a significant improvement in control of rhinorrhea, congestion, and sneezing compared with baseline over the 6 months of treatment (P < .05). Only for the control of sneezing was BDP consistently better than IB (P < .05). Among the patients given IB, 61% to 73% assessed the control of rhinorrhea as good or excellent on different study visit days, 43% to 60% similarly rated the control of nasal congestion, and 39% to 43% the control of sneezing. The results for BDP were 68% to 78% for the control of rhinorrhea, 55% to 72% for the control of nasal congestion, and 54% to 68% for the control of sneezing. Quality of life assessment documented that both drugs significantly reduced interference with daily activities and disturbance of mood due to rhinorrhea compared with baseline (P < .05). Both treatments were well tolerated with IB causing less nasal bleeding and irritation than BDP.nnnCONCLUSIONSnIpratropium bromide was safe and effective in controlling rhinorrhea and diminishing the interference by rhinorrhea in school attendance, concentration on school work, and sleep. Ipratropium bromide was as effective as BDP in the control of rhinorrhea and showed a relatively good effect on congestion. Patient and physician assessment favored BDP in the control of sneezing.

Measuring Adherence with the Doser CT in Children with Asthma

Non‐adherence with prescribed asthma treatment causes compromised treatment effectiveness, including greater morbidity, mortality, and health care utilization costs. As a result, there is an increasing interest in measuring patient adherence behaviors. Electronic monitoring devices offer a promising method for assessing patient adherence behavior patterns. The reliability of the Doser Clinical Trials (CT) (Meditrack Products, Hudson, MA), an inexpensive, pressure‐actuated device that monitors metered‐dose inhaler (MDI) usage, was evaluated in a field study of outpatient pediatric asthmatics. Canister weight and various Doser CT measures of patient medication use were compared to determine the reliability and usefulness of the device. Doser CTs were dispensed to 16 research subjects for use on corticosteroid MDIs over a period of several months. One Doser CT per month was dispensed to each subject. Doser CTs were collected at 30–60 day intervals, with a total of 61 months of Doser CT data obtained across the subjects. MDI canister weights were monitored for a subset of 6 subjects. Usable Doser CT data were summarized and average adherence estimates were computed. Adherence estimates differed from one another and the adherence estimate, as measured by canister weight, was significantly higher than each Doser CT estimate. However, overall, the Doser CT showed adequate reliability as evidenced by high correlations among the Doser CT estimates of adherence and the existing gold standard of canister weight. The Doser CT is likely to be useful for monitoring MDI use in clinical care and research, potentially providing greater accuracy than the standard of canister weight.

Reliability of the model MC-311 MDI Chronolog

BACKGROUNDnThe Model MC-311 MDI Chronolog (Medtrac Technologies, Lakewood, Colo) is an electronic device for monitoring adherence to metered-dose inhalers (MDIs). It is a thermistor-actuated, microprocessor-equipped device that dispenses inhaled medication while recording the date and time of each canister activation.nnnOBJECTIVEnWe evaluated the reliability of the MC-311 MDI Chronolog to determine whether the model could accurately record and report the date, time, and number of MDI actuations.nnnMETHODSnTwenty-four of the MC-311 Chronologs were discharged at 8 hourly intervals across 8 days. Battery voltage was assessed before and after the experiment. The mouthpieces of 12 Chronologs were washed daily.nnnRESULTSnBy using generous criteria for acceptable reliability, only 10 of 24 (42%) were rated as acceptable. None of these 10 Chronologs recorded 320 or greater actuations (mean +/- SD, 293.9 +/- 13.3; range, 266 to 308); all reliable Chronologs underestimated MDI activation. An additional 6 devices had an initial signature of erroneous recordings dating from device initialization. After removing this signature, the remaining data showed acceptable reliability. All the remaining Chronologs judged to be unacceptable showed time series patterns of seizures (ie, bursts of clustered, erroneous records). Seizures were distributed across trial days, were associated with washing, and preceded all 4 cases of battery failure. Damage to the thermistor is the likely cause of seizure-pattern failures.nnnCONCLUSIONSnIn summary, because of a combination of a clear underreporting bias with frequent initialization and seizure-pattern failures, the Model MC-311 MDI Chronolog is not recommended for use in clinical care or research

Safety and tolerability of omalizumab in children with allergic (IgE-mediated) asthma

Abstract Objective: This pooled analysis assessed the safety of omalizumab in children with allergic (immunoglobulin E-mediated) asthma. Study design: Two double-blind, placebo-controlled studies in children (6 to <u200912 years) with moderate-to-severe allergic asthma investigated the efficacy/safety of omalizumab. Children on optimized asthma care (inhaled corticosteroidsu2009±u2009other controller medications) were randomized (2:1) to omalizumab (75–375u2009mgu2009sc, q2 or q4wk) or placebo. Pooled safety findings from these trials are presented in this publication. Results: The safety population included 926 children (omalizumab, nu2009=u2009624; placebo, nu2009=u2009302). Adverse events (AEs) were more frequently reported in the placebo (91.7%) than omalizumab (89.7%) group. The most common AEs were nasopharyngitis, upper respiratory tract infection and headache. Suspected treatment-related AEs included headache, erythema and urticaria; none of which were reported by ≥2% of patients receiving omalizumab. Serious AEs (SAEs) were reported by 3.4% and 6.6% of patients receiving omalizumab and placebo, respectively; the most common were appendicitis, pneumonia and bronchitis; no deaths were reported. Conclusions: Omalizumab has an acceptable safety profile, with a risk of AEs similar to placebo. This, combined with its efficacy profile, suggests that omalizumab may provide an additional asthma management option for children (6 to <u200912 years) uncontrolled with current therapy that follows established guidelines.

Ipratropium Nasal Spray in Children with Perennial Rhinitis

OBJECTIVEnTo compare the efficacy and safety of ipratropium nasal spray and placebo administered twice each day for 4 weeks in pediatric patients with perennial rhinitis who had rhinorrhea as a major complaint.nnnMETHODSnThis was a multicenter, double-blind, parallel group study. Patients aged 6 to 18 years with symptoms of perennial nonallergic (PNAR) or perennial allergic rhinitis (PAR) were randomized to receive ipratropium (42 micrograms per nostril) or placebo nasal spray, double-blind, twice each day for 4 weeks. Efficacy was evaluated by nasal symptoms, especially anterior rhinorrhea, and quality of life. Previous caregivers for rhinitis and medications used in the past were also evaluated.nnnRESULTSnA total of 202 patients were empanelled, 162 with PAR, 40 with PNAR; of these 151 with mild-severe rhinorrhea were evaluated for efficacy. Treatment with ipratropium reduced symptoms of rhinorrhea primarily in patients with PNAR. In patients with PAR this response was less pronounced, and was seen as a modest decrease in the severity of rhinorrhea noted in the first 2 weeks of treatment. Quality of life assessments confirmed that rhinorrhea was bothersome to these pediatric patients, and suggested that treatment with ipratropium nasal spray was associated with an improvement, especially in the patients with PNAR. There were few adverse events; these were similar in the two treatment groups.nnnCONCLUSIONSnIpratropium nasal spray 0.03% administered at a dose of 42 micrograms/nostril bid is a safe and effective new therapy for control of anterior rhinorrhea in pediatric patients with PNAR. Twice daily administration is adequate for patients with PNAR, but patients with PAR might benefit from more frequent administration (e.g., tid).

Adverse Effects of Medications for Rhinitis

LEARNING OBJECTIVESnReading this article will reinforce the readers awareness of the adverse effects of medications used for the treatment of rhinitis.nnnDATA SOURCESnArticles on therapy of rhinitis and reports of associated side effects were reviewed. A MEDLINE database using subject keywords was searched from 1992 through 1997.nnnSTUDY SELECTIONnPertinent articles were chosen. A distinction was made in the text between controlled studies and case reports.nnnRESULTSnAntihistamines, decongestants, anticholinergic agents, and corticosteroids, alone or in combination are used in the treatment of rhinitis. Reported side effects include sedation, psychosis, impaired learning and memory, and cardiac arrhythmias.nnnCONCLUSIONnRhinitis and its complications are important medical conditions. Adverse reactions are often difficult to diagnose and assess. Side effects may arise from the use of individual drugs or from drug combinations. There is insufficient cause to abandon these medications, but physicians must be mindful of the inherent risks of the drugs that they prescribe and of others that their patients may be taking without the physicians knowledge or approval.

Exercise-induced anaphylaxis related to specific foods

We describe the case, documented by challenge results, of a 16-year-old girl with exercise-induced anaphylaxis associated with eating pizza and a cheese sandwich. Patients in whom a specific coprecipitating food has been identified should avoid it for at least 12 hours before exercise. All patients should be instructed to avoid eating 6 to 8 hours before exercise, discontinue exercise at the first sign of symptoms, and exercise only with a companion prepared to administer epinephrine.