### Therapy Scenario

You are a school nurse who regularly visits a number of elementary and middle schools (children aged 5 to 13 years) in your region. It is cold and flu season once again. One of the teachers stops you in the hall to ask you a question about his 10- year old daughter who also has a cold. He has heard that zinc lozenges can help to relieve cold symptoms and wonders if they really do work and if it is OK to give them to children.

With him you formulate the question, in children with colds are zinc lozenges safe and effective for relief of cold symptoms?

Searching terms and evidence source:
You do a search of the Cochrane database (Issue 1, 1999) to see if any systematic reviews are available on the topic. Using the search terms “zinc” and “cold”, you find no reviews. You then do a quick search of Best Evidence 3 using the same search terms and find 1 study that looked at the effectiveness of zinc lozenges for colds – unfortunately, the sample consisted of adults only. Not to be discouraged, you decide to do a search in MEDLINE using PubMed (available on the Internet). You do an Advanced Search using the terms “zinc AND cold” and come up with 233 citations – a bit more than you have time to review. You add the search term “child” to your previous search and your search result is reduced to 13 citations. Having been a good student of critical appraisal, you know that the best evidence to support a decision about treatment effectiveness usually comes from randomized controlled trials. So once more, you limit your search result by adding the term “randomized controlled trial” – 4 trials remain. One of these trials, a study by Macknin et al ( JAMA 1998;279:1962-7 ) seems to be right on target.

• Is the evidence from this randomised trial valid?
• If valid, is this evidence important?
• If valid and important, can you apply this evidence in caring for your patient?

### Completed Therapy Worksheet for Evidence-Based Nursing

#### Citation

Macknin ML, Piedmonte M, Calendine C, Janosky J, Wald, E. Zinc gluconate lozenges for treating the common cold in children. A randomized controlled trial. JAMA 1998;279:1962-7

#### Are the results of this single preventive or therapeutic trial valid?

Was the assignment of patients to treatments randomised?
And was the randomisation list concealed?
Yes
Yes. Computer generated randomisation code given to pharmacist who prepared medication packages.
Were all patients who entered the trial accounted for at its conclusion? -and were they analysed in the groups to which they were randomised?
Yes, all children were accounted for. 117/124 children (94%) allocated to the intervention completed the trial and 122/125 children (98%) allocated to placebo completed the trial. Authors stated that analyses were conducted using intention-to-treat principles.
Were patients and clinicians kept “blind” to which treatment was being received?
Yes, both study personnel and participants were blinded to allocation. Medication packages were identical in appearance except for the identifying code.
Aside from the experimental treatment, were the groups treated equally?
Yes.
Were the groups similar at the start of the trial?
At baseline, groups were similar for age; sex; race; body surface area; allergies; smoking; smoking in the home; history of colds, infections, and complications; and temperature. 25% of the intervention group took vitamin supplements compared with 16% of the placebo group (p=0.08). Students were asked to stop taking zinc-containing vitamins or mineral supplements during the study. 7.5% of the intervention group had a history of asthma compared with 14% of the placebo group (p=0.10); analysis showed that this imbalance had no effect on outcome.

#### Are the valid results of this randomised trial important?

Main outcome was time to resolution of cold symptoms. Secondary outcomes included school absences and adverse effects.

Median time to resolution of cold symptoms did not differ between groups (9 days for both groups). {Because time to resolution of cold symptoms is a continuous variable, RRR, ARR, NNT cannot be calculated.}

School absences
(number of children with absences)
Relative Risk Reduction
RRR
Absolute Risk Reduction
ARR
Number Needed to Treat
NNT
Placebo
CER
Zinc lozenges
EER
(CER-EER)/CER CER-EER 1/ARR
20.8% 18.5% (20.8%-18.5%)/20.8%
= 11.1%
95% CI -46.7 to 45.9
20.8% – 18.5%
= 2.3%
1/2.3%
= 44 pts
95% CI 8 to infinity
(e.g., bad taste reactions; nausea; mouth, tongue or throat irritation; and diarrhoea)
Relative Risk Increase
RRI
Absolute Risk Increase
ARI
Number Needed to Harm
NNH
Placebo
CER
Zinc lozenges
EER
(CER-EER)/CER CER-EER 1/ARI
79.8% 98.6% (79.8%-88.6%)/79.8%
= 11.0%
95% CI -21.7 to 3.7
79.8% – 88.6%
= 8.8%
1/8.8%
= 11 pts
95% CI 6 to infinity

#### Can you apply this valid, important evidence about a treatment in caring for your patient?

##### Do these results apply to your patient?
Similar – Grades 1 to 12 students in 2 suburban school districts in Cleveland, Ohio, USA.
How great would the potential benefit of therapy actually be for your individual patient?
Method I:

Risk of the outcome (school absence) in your patient, relative to patients in the trial. expressed as a decimal: 1

$$mathit{NNT}/mathit{f} = 44/1 = 44 text{ (95%CI 8 to infinity)}\\ text{(NNT for patients like yours)}$$

Method II: 1 / (PEER x RRR)

Your patient’s expected event rate if they received the control treatment: PEER:______

$$1 / (mathit{PEER} times mathit{RRR}) = 1/underline{qquadqquad} = underline{qquadqquad}\\ text{(NNT for patients like yours)}$$

##### Are your patient’s values and preferences satisfied by the regimen and its consequences?
Do your patient and you have a clear assessment of their values and preferences?
Patient values/preferences unknown but these could be discussed with the child and parent; however, I would want a treatment that does more good than harm.
Are they met by this regimen and its consequences?
No (based on my values/preferences) – no apparent benefit in terms of symptom relief and school absences, and potential for adverse effects.

Interestingly, the article that you identified from your search of Best Evidence that evaluated the effectiveness of zinc lozenges in adults with cold symptoms found that zinc lozenges WERE effective. (see Mossad SB, Macknin ML, Medendorp SV, Mason P. Zinc gluconate lozenges for treating the common cold. A randomized, double-blind, placebo-controlled study. Ann Intern Med. 1996;125:81-8).

### Cold symptoms: Zinc lozenges did not reduce cold symptoms in children and adolescents

#### Clinical Bottom Line

Zinc gluconate lozenges were not effective for reducing symptoms of the common cold in children and adolescents.

#### Citation

Macknin ML, Piedmonte M, Calendine C, Janosky J, Wald, E. Zinc gluconate lozenges for treating the common cold in children. A randomized controlled trial.
JAMA 1998;279:1962-7

#### Clinical Question

In school age children with colds, are zinc lozenges safe and effective for relief of cold symptoms?

#### Search Terms

Medline (using PubMed) with the search terms zinc AND cold* AND child* AND randomized controlled trial.

#### The Study

• Double-blinded concealed randomised controlled trial with intention-to-treat.
• Students in Grades 1 to 12 (median age 13 y) who had at least 2 of the following symptoms within the previous 24 hours: cough, headache, hoarseness, muscle ache, nasal congestion, nasal drainage, scratchy throat, sore throat, or sneezing.
• Control group (n=125): 3.75 g hard candy lozenges containing sucrose, corn syrup, aminoacetic acid, cherry flavouring oils and placebo (calcium lactate pentahydrate). All students took 3 lozenges each school day; students in grades 1-6 took 2 lozenges each night, and 5 each day on the weekend; students in grades 7 – 12 took 3 lozenges each school night and 6 each day on the weekend. Students were given enough lozenges for 21 days of treatment and instructed to take the lozenges until their cold symptoms completely resolved for 6 hours.
• Experimental group(n=124): Same as for control regimen except that lozenges contained zinc gluconate trichydrate, 10 mg instead of placebo.

#### The Evidence

Outcome Time to Outcome RRR 95% CI ARR 95% CI NNT 95% CI
School absences (number of children) N/A 10% -38% to 57% 0.020 -0.080 to 0.120 50 NNH = 13 to INF;
NNT = 8 to INF
At least 1 adverse effect Resolution of symptoms -12% (RRI) -23% to 0% -0.092 (ARI) -0.182 to -0.002 -11 (so an NNH of 11) -441 to -6