A Randomized Trial of a Multicomponent Intervention to Promote Medication Adherence: The Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial (TAKE-IT).

2018

2018 Mar 15

1523-6838

<p><strong>BACKGROUND: </strong>Poor adherence to immunosuppressive medications is a major cause of premature graft loss among children and young adults. Multicomponent interventions have shown promise but have not been fully evaluated.</p>

<p><strong>STUDY DESIGN: </strong>Unblinded parallel-arm randomized trial to assess the efficacy of a clinic-based adherence-promoting intervention.</p>

<p><strong>SETTING &amp; PARTICIPANTS: </strong>Prevalent kidney transplant recipients 11 to 24 years of age and 3 or more months posttransplantation at 8 kidney transplantation centers in Canada and the United States (February 2012 to May 2016) were included.</p>

<p><strong>INTERVENTION: </strong>Adherence was electronically monitored in all participants during a 3-month run-in, followed by a 12-month intervention. Participants assigned to the TAKE-IT intervention could choose to receive text message, e-mail, and/or visual cue dose reminders and met with a coach at 3-month intervals when adherence data from the prior 3 months were reviewed with the participant. "Action-Focused Problem Solving" was used to address adherence barriers selected as important by the participant. Participants assigned to the control group met with coaches at 3-month intervals but received no feedback about adherence data.</p>

<p><strong>OUTCOMES: </strong>The primary outcomes were electronically measured "taking" adherence (the proportion of prescribed doses of immunosuppressive medications taken) and "timing" adherence (the proportion of doses of immunosuppressive medications taken between 1 hour before and 2 hours after the prescribed time of administration) on each day of observation. Secondary outcomes included the standard deviation of tacrolimus trough concentrations, self-reported adherence, acute rejection, and graft failure.</p>

<p><strong>RESULTS: </strong>81 patients were assigned to intervention (median age, 15.5 years; 57% male) and 88 to the control group (median age, 15.8 years; 61% male). Electronic adherence data were available for 64 intervention and 74 control participants. Participants in the intervention group had significantly greater odds of taking prescribed medications (OR, 1.66; 95% CI, 1.15-2.39) and taking medications at or near the prescribed time (OR, 1.74; 95% CI, 1.21-2.50) than controls.</p>

<p><strong>LIMITATIONS: </strong>Lack of electronic adherence data for some participants may have introduced bias. There was low statistical power for clinical outcomes.</p>

<p><strong>CONCLUSIONS: </strong>The multicomponent TAKE-IT intervention resulted in significantly better medication adherence than the control condition. Better medication adherence may result in improved graft outcomes, but this will need to be demonstrated in larger studies.</p>

<p><strong>TRIAL REGISTRATION: </strong>Registered at ClinicalTrials.gov with study number NCT01356277.</p>

10.1053/j.ajkd.2017.12.012

29602631

Germline genetic variation and treatment response on CCG-1891.

2012

695-700

2012 May

1545-5017

<p><strong>BACKGROUND: </strong>Recent studies suggest that polymorphisms in genes encoding enzymes involved in drug detoxification and metabolism may influence disease outcome in pediatric acute lymphoblastic leukemia (ALL). We sought to extend current knowledge by using standard and novel statistical methodology to examine polymorphic variants of genes and relapse risk, toxicity, and drug dose delivery in standard risk ALL.</p>

<p><strong>PROCEDURE: </strong>We genotyped and abstracted chemotherapy drug dose data from treatment roadmaps on 557 patients on the Children's Cancer Group ALL study, CCG-1891. Fourteen common polymorphisms in genes involved in folate metabolism and/or phase I and II drug detoxification were evaluated individually and clique-finding methodology was employed for detection of significant gene-gene interactions.</p>

<p><strong>RESULTS: </strong>After controlling for known risk factors, polymorphisms in four genes: GSTP1*B (HR = 1.94, P = 0.047), MTHFR (HR = 1.61, P = 0.034), MTRR (HR = 1.95, P = 0.01), and TS (3R/4R, HR = 3.69, P = 0.007) were found to significantly increase relapse risk. One gene-gene pair, MTRR A/G and GSTM1 null genotype, significantly increased the risk of relapse after correction for multiple comparisons (P = 0.012). Multiple polymorphisms were associated with various toxicities and there was no significant difference in dose of chemotherapy delivered by genotypes.</p>

<p><strong>CONCLUSIONS: </strong>These data suggest that various polymorphisms play a role in relapse risk and toxicity during childhood ALL therapy and that genotype does not play a role in adjustment of drug dose administered. Additionally, gene-gene interactions may increase the risk of relapse in childhood ALL and the clique method may have utility in further exploring these interactions. childhood ALL therapy.</p>

10.1002/pbc.23192

Pediatr Blood Cancer

21618417

Shifting place of death among children with complex chronic conditions in the United States, 1989-2003.

2007

2725-32

06/2007

1538-3598

<p><strong>CONTEXT: </strong>The place where children with complex chronic conditions are dying may be shifting toward residential homes due to the evolving epidemiology of life-threatening childhood conditions, advances in home-based medical technology, and changes in attitudes about pediatric palliative care and hospice services.</p>

<p><strong>OBJECTIVES: </strong>To determine whether pediatric deaths attributed to complex chronic conditions are increasingly occurring in the home and to assess race and ethnicity disparities in the location of death.</p>

<p><strong>DESIGN, SETTING, AND PARTICIPANTS: </strong>Retrospective national-level case series drawn from the National Center for Health Statistics' Multiple Cause of Death Files spanning 1989-2003. Participants included all deceased individuals aged 19 years or younger with a complex chronic condition excluding injury and noncomplex chronic conditions (as classified by International Classification of Diseases, Ninth Revision or International Classification of Diseases, Tenth Revision).</p>

<p><strong>MAIN OUTCOME MEASURE: </strong>Place where death occurred.</p>

<p><strong>RESULTS: </strong>Among the 22.1% of deaths (198 160 of 896 509 total deaths) attributed to a complex chronic condition between 1989 and 2003, the percentage of individuals dying at home increased significantly (P&lt;.001) over time for infants (aged &lt;1 year) (4.9% in 1989 and 7.3% in 2003); 1- to 9-year-olds (17.9% and 30.7%); and for 10- to 19-year-olds (18.4% and 32.2%). Adjusting for decedent characteristics, the odds of dying at home increased significantly each year (odds ratio, 1.04; 95% confidence interval, 1.03-1.04) and were reduced among both black and Hispanic decedents (odds ratio, 0.50; 95% confidence interval, 0.48-0.52 and odds ratio, 0.52; 95% confidence interval, 0.50-0.54, respectively) compared with white decedents.</p>

<p><strong>CONCLUSIONS: </strong>Children who die with underlying complex chronic conditions increasingly are dying at home. Racial and ethnic disparities regarding place of death may represent important limitations and opportunities for improvement in the current systems of pediatric chronic and palliative care.</p>

10.1001/jama.297.24.2725

JAMA

17595273