Impact of Nursing Interventions on Adherence to Treatment With Anti-tuberculosis Drugs in Children and Adolescents

This study evaluates the efficacy of nursing interventions on adherence to antituberculosis medication in a paediatric cohort (aged 0-18 years) and identifies the risk factors for non-compliance.

There are two phases in the study; Phase 1: retrospective descriptive analysis in children and young people receiving antituberculosis treatment (non-intervention group); and Phase 2: quasi-experimental, longitudinal, prospective study (intervention group). The results of the two phases will be compared.

The study was carried out in the outpatient tuberculosis (TB) Unit of a tertiary-care pediatric center in Catalonia (Northeast Spain), which is a referral center for pediatric TB (Hospital Sant Joan de Déu) in the Southern Barcelona Health Care Region (Regió Sanitària Barcelona Sud) (1,346,000 inhabitants, 16.5% of whom are under 18 years of age).The TB incidence rate in Catalonia has decreased from 21.6 per 100,000 population in 2004 to 14.4 in 2015 (7.3 cases per 100,000 population of pediatric age)(Rodés, Espinilla, \& García, 2016).

In both phases, all children and adolescents (aged \<18 years) starting anti-tuberculosis (anti-TB) treatment due to close contact with a TB patient (primary chemoprophylaxis), Latent Tuberculosis Infection (LTBI) or TB disease were eligible to participate in the study. Directly Observed Treatment (DOT) is not routinely available in Spain, and its use is restricted to individual cases, as per physician decision.

The number of children and adolescents required to participate in the study was calculated using a unilateral chi-square proportion comparison test for independent samples, with a level of significance of 5% and a power of 80%, a 2/1 ratio in Phase 1/Phase 2 group sizes and assuming a significant increase of 15% in the adherence rate after the nurse-led interventions (60% in Phase 1 and 75% in Phase 2). Thus, it was calculated that 182 and 91 children and adolescents would be needed in the Phase 1 and Phase 2 groups, respectively.

Procedure and interventions:

As per national guidelines, primary chemoprophylaxis after TB contact consists of isoniazid in monotherapy until TB infection screening is repeated 10-12 weeks later. Treatment of LTBI includes either 3 months of isoniazid and rifampicin or 6-9 months of isoniazid in monotherapy, and treatment of TB disease consists of a 2-month induction phase with 4 drugs (isoniazid, rifampicin, pyrazinamide and ethambutol), followed by isoniazid and rifampicin for a minimum of 4 months.

Routine outpatient follow-up visits were scheduled as follows: (a) in patients receiving primary chemoprophylaxis or LTBI treatment: baseline visit, and 2 weeks and 3 months later (end of treatment in most cases); (b) in patients treated for TB disease: baseline visit, 2 weeks later and on a monthly basis thereafter.

Four nurse-led interventions were implemented after Phase 1: 2 educational interventions (leaflet in mother tongue and a follow-up open telephone call) and 2 monitoring interventions (the Eidus-Hamilton test and a written questionnaire about adherence to anti-TB treatment), which were exclusively carried out by 2 study nurses.

Whenever the Eidus-Hamilton test or the written questionnaire were consistent with sub-optimal adherence, immediate feedback was given to the parents and the patient the study nurse underlined the importance of adherence, assessed any potential hindrances and answered any questions. A follow-up visit or telephone call was scheduled 7-10 days later.

The level of adherence to anti-TB treatment was be identified retrospectively in Phase 1 of the study, as the risk factors associated with adherence in our cohort. Once Phase 2 was completed, the results were be compared with those of Phase 1 and the success of the new nurse-led interventions assessed.

Final results will be used to design the definitive Nurse-led Follow-up Programme that will be implemented in the TB Unit.

Eligibility Criteria:
Inclusion Criteria:

* In both phases, all children and adolescents (aged \<18 years) starting anti-TB treatment due to close contact with a TB patient (primary chemoprophylaxis), Latent Tuberculosis Infectious (LTBI) or Tuberculosis (TB) disease were eligible to participate in the study.

Exclusion Criteria:

* Referral from another center after anti-TB treatment had already begun
* Patients with other chronic diseases requiring hospital follow-up and/or other chronic therapies
* Known poor previous adherence to anti-TB treatment (if treatment was repeated or restarted)
* A significant language barrier that prevented the child or his/her relatives from properly understanding the nature of the study.