Objective: Most children with endocrine diseases require long-term continuity of care. We investigated the prevalence of loss to follow-up (LTFU) in pediatric patients with chronic endocrine diseases and the risk factors associated with LTFU. Methods: This observational cohort study included all children with chronic endocrine diseases included in the database of a single academic pediatric care center over a period of 8 years. LTFU was defined as a lack of attendance at clinical visits for over 2 years, for unknown reasons. Results: LTFU was recorded for 154 of the 1,067 patients included (14%). Median age at diagnosis was 5.8 (0.3–11.8) vs. 1.2 (0.0–6.9) years, and age at last visit was 14.1 (9.7–16.1) vs. 11.7 (6.1–15.8) years, for the LTFU and no-LTFU groups, respectively. In multivariate analysis, the risk of LTFU increased with age at diagnosis (OR 1.18; 95% CI 1.12–1.24) and was higher for patients diagnosed before 2006 (vs. after 2006; OR 4.80; 95% CI 3.00–7.66), with fewer visits in the last 3 years (OR 0.72; 95% CI 0.65–0.80; p < 0.0001) and a lower health insurance classification (OR 1.79; 95% CI 1.10–2.89; p = 0.02). The risk of LTFU was higher for patients with isolated growth hormone deficiency than for those with other endocrine conditions, such as multiple pituitary deficiencies, hypogonadotropic hypogonadism, Turner syndrome, or thyroid, adrenal, or gonadal disorders (OR 5.24; 95% CI 1.13–24.37; p = 0.03). Conclusion: This study provides the first epidemiological data for LTFU in children and adolescents with chronic endocrine diseases. It should facilitate the targeting of interventions to improve adherence to medical care and healthcare organization during the pediatric period.

The diagnosis and prognosis of most chronic conditions with a childhood onset have improved considerably over the last few decades in high-income countries [1, 2]. Most patients with endocrine diseases diagnosed during childhood require long-term continuity of care. A lack of regular medical follow-up visits may be associated with poorer long-term health outcomes, with greater risks of morbidity and mortality [2]. Reported dropout rates following the transition to adult healthcare services range from 3 to 37%, depending on the chronic endocrine disorder considered [3]. The importance and challenges of the transition from pediatric to adult healthcare are well recognized [4-7] but few studies have considered loss to follow-up (LTFU) during pediatric care [8-14], despite the importance of adherence to medical care in a context of successful clinical management for health, growth, and development in children.

The identification of children and adolescents lost to follow-up and of the factors associated with LTFU is important because it could help to target interventions for improving adherence to medical care and optimizing long-term prognosis [15, 16]. Such information could also improve our understanding of the epidemiology of LTFU and the organization of pediatric healthcare.

We investigated the prevalence of LTFU during pediatric care, in patients with chronic endocrine diseases, to identify the risk factors associated with LTFU.

Patients

This observational cohort study included all pediatric patients with chronic endocrine diseases included in the database of a single academic pediatric care center between January 2007 (for reasons of database quality) and June 2014, with a study end point in December 2016. All the patients were under the age of 16 years in January 2007.

Patients were considered eligible for the study if they were included in the database of our reference center for endocrine growth and developmental disorders: patients with non-acquired isolated or multiple pituitary deficiencies, congenital hypothyroidism, Graves’ disease, Turner syndrome, congenital adrenal insufficiency, or disorders of sex development (DSD). For most patients, at least one visit to the clinic per year is required for optimal follow-up. At each visit, the parents are requested to take the following appointment for their child. If a patient fails to attend a scheduled visit, we send a letter to the parents proposing another appointment. If the patient does not attend this visit either, we write to the patient’s general practitioner to inform him or her of the patient’s failure to attend medical visits and to ask him or her to contact the patient and the family to explain the need for regular visits to the expert center to improve outcome.

LTFU was defined as a lack of attendance at clinical visits for at least 2 years, for unknown reasons, except for patients with congenital hypogonadotropic hypogonadism or DSD, for whom such frequent clinical care is unnecessary during the prepubertal period after initial management. For these patients, LTFU was defined as an absence of clinical visits after the age of 13 years for girls and 14 years for boys, or not returning to the clinic after the age of 15 years for girls and 16 years for boys, as these patients require careful assessment during the pubertal period due to the requirement for long-term sex hormone replacement and/or a high risk of gonadal insufficiency or of a deterioration of gonadal function over time.

We initially identified 1,463 patients from the database as eligible for inclusion in this study. We excluded those who stopped attending the clinic for known reasons, such as transfer to another pediatric (n = 91) or adult (n = 137) center, referral to our clinic for a single visit to obtain an expert opinion (n = 32), death (n = 6), or demonstration of a reversible condition (n = 130), such as those with transient isolated growth hormone deficiency (IGHD) or congenital hypothyroidism, or Grave’s disease in remission. The final study population consisted of 1,067 patients and the selection of the study population is illustrated in a flowchart (Fig. 1).

Fig. 1.

Flowchart of the study.

Fig. 1.

Flowchart of the study.

Close modal

Study Protocol

The demographic characteristics recorded included sex, year (before or after 2006) and age at diagnosis, age at last visit and at study end point (over or under 15 years), duration of follow-up (<2 years, between 2 and 4 years, >4 years), number of visits during the last 3 years of follow-up, presence or absence of a prescription for hormonal treatment at the last visit, country of birth (France vs. other countries), and health insurance system scheme (the standard medical insurance regime or a regime for disadvantaged individuals). The last 3 of these variables were obtained from the patient’s computerized medical records.

The study protocol was approved by the Ethics Review Committee for Biomedical Research Projects Robert Debré University Hospital (No. 2017-342). Informed consent was obtained from the parents.

Methods

Patients were classified into 9 subgroups on the basis of their chronic endocrine pathological conditions: idiopathic IGHD; multiple pituitary insufficiency including non-acquired multiple anterior pituitary insufficiencies and craniopharyngioma; congenital hypogonadotropic hypogonadism; congenital hypothyroidism; Graves’ disease; Turner syndrome; congenital adrenal insufficiency; idiopathic 46,XY DSD; non-idiopathic DSD including gonadal dysgenesis, testis regression, ovotesticular DSD, disorders of androgen action, and persistent Müllerian duct syndrome.

Growth hormone deficiency was considered transient if peak serum growth hormone concentration was at least 20 mIU/L in a pharmacological stimulation test after the cessation of growth hormone treatment [17]. Patients who were not reassessed for growth hormone secretion after growth hormone treatment were considered to have a persistent growth hormone deficiency. Transient forms of congenital hypothyroidism included a normally located thyroid gland with levothyroxine treatment initiated during the neonatal period, with normal thyroid function after the cessation of treatment after the age of 6 months [18]. Patients with Graves’ disease were considered to be in remission if they had normal thyroid function after the cessation of antithyroid drug therapy for at least 2 years [19].

The year of diagnosis was classified into 2 periods: before and after 2006 (year in which our reference center for rare endocrine growth and developmental disorders was set up, with a therapeutic education nurse who sees the patients at their first referral to the center and thereafter, if required, during follow-up).

All patients resident in France were covered by the French national health insurance system [20]. We considered 2 categories of health insurance, to obtain an index of the social categories of the patients concerned: the general or specific national health insurance system, and 3 types of health insurance corresponding to patients from more disadvantaged backgrounds receiving social assistance (18% of our cohort): AME (Aide medical d’Etat, the provision of basic healthcare to foreigners without French papers), CMU (Couverture Maladie Universelle, universal healthcare for students and low-earners), and CMUc (Couverture Maladie Universelle-complémentaire, complementary health insurance for students and low-earners).

Statistical Analysis

The results are expressed as numerical values (percentages) for categorical variables and as medians (25–75th percentiles) for continuous variables. Two groups were compared: patients lost to follow-up for unknown reasons and patients with appropriate follow-up.

Missing values were replaced by a multiple imputation procedure based on the Monte Carlo method, using the following data (number of missing values specified for each variable): sex (0), pathological condition (0), age at diagnosis (17), type of health insurance (67), hormonal treatment prescription at last visit (1), number of visits during the last 3 years of follow-up (0), age at last visit (0), and country of birth (31).

Factors explaining the event (LTFU) were identified in logistic regression models. All variables were adjusted for sex, except for 2 sex-dependent conditions: Turner syndrome and idiopathic 46,XY DSD. Univariate analysis was first performed to determine the crude association of each factor with the event of interest. The factors significant at the 20% level in univariate analysis were then selected for inclusion in the multivariate model. The final model was obtained by automatically selecting the factors significant at the 5% level in a stepwise method.

For analysis of the effect of treatment, which depends on the endocrine disease, we estimated 7 multivariate models, one for each condition considered. Two diseases were not considered in this analysis because all patients are treated: congenital adrenal insufficiency and congenital hypothyroidism. The selected factors were those used in the global multivariate model, plus treatment. Automatic selection was used to retain only significant factors for the multivariate analysis. The factor “treatment” was forced into the model. Bonferroni correction for multiple testing was performed. For this analysis of treatment effect, values of 0.007 or below (0.7%) were considered significant.

Statistical significance was defined as p < 0.05. The analyses were conducted with SAS software (version 9.4, SAS Institute Inc., Cary, NC, USA).

In total, 154 of the 1,067 patients studied (14%) were lost to follow-up (Fig. 1). The median (25–75th percentile) follow-up period for the 1,067 patients was 5.9 (3.2–9.9) years, and the characteristics of the patients are shown in Table 1 and Figure 2, by endocrine disease and follow-up status (LTFU vs. appropriate follow-up). The proportion of patients lost to follow-up was higher for patients with IGHD (22%) and idiopathic 46,XY DSD (23%), and lower in patients with congenital adrenal insufficiency (3%) than in the other pathological groups. Median age at diagnosis was 5.8 (0.3–11.8) vs. 1.2 (0.0–6.9) years, age at the last visit was 14.1 (9.7–16.1) vs. 11.7 (6.1–15.8) years, median follow-up was 4.3 (1.9–9.1) vs. 6.0 (3.5–10.1) years at the end of the study period, and the number of visits during the last 3 years was 4.0 (3.0–6.0) vs. 6.0 (4.0–7.0) for patients in the LTFU and appropriate follow-up groups, respectively. The median duration of follow-up varied considerably between pathological conditions, from 1.6 (0.6–2.3) years for congenital hypogonadotropic hypogonadism to 11.4 (3.2–16.3) years for non-idiopathic DSD patients lost to follow-up.

Table 1.

Demographic and clinical characteristics of the total study population

Demographic and clinical characteristics of the total study population
Demographic and clinical characteristics of the total study population
Fig. 2.

Patient distribution by endocrine disease.

Fig. 2.

Patient distribution by endocrine disease.

Close modal

We performed a logistic regression analysis on clinical variables, to identify factors predictive of LTFU (Table 2). Univariate analysis revealed that LTFU was significantly associated with higher age at diagnosis and at the study end point, diagnosis before 2006, a duration of follow-up until the last visit of <2 years, pathological subgroup, not being on hormone replacement therapy at the last visit, fewer visits during the last 3 years of follow-up, and a lower health insurance classification. Sex and country of birth were not significant.

Table 2.

Uni- and multivariate models analyzing loss to follow-up during the pediatric period for patients with endocrine conditions

Uni- and multivariate models analyzing loss to follow-up during the pediatric period for patients with endocrine conditions
Uni- and multivariate models analyzing loss to follow-up during the pediatric period for patients with endocrine conditions

In the multiple logistic regression model, the risk of LTFU remained significantly associated with higher age at diagnosis (OR 1.18; 95% CI 1.12–1.24), diagnosis before 2006 (vs. after 2006; OR 4.80; 95% CI 3.00–7.66), fewer visits during the last 3 years (OR 0.72; 95% CI 0.65–0.80; p < 0.0001), and lower health insurance classification (OR 1.79; 95% CI 1.10–2.89; p = 0.02). The risk of LTFU was higher for patients with IGHD than for those with other endocrine diseases, such as multiple pituitary deficiencies, hypogonadotropic hypogonadism, thyroid, Turner syndrome, or adrenal or gonadal disorders (OR 5.24; 95% CI 1.13–24.37; p = 0.03).

The risk of LTFU was not associated with the prescription of hormonal treatment at the last visit when patients were analyzed by pathological condition (data not shown). Sex was not analyzed because some of the endocrine diseases considered were sex specific (i.e., Turner syndrome and idiopathic 46,XY DSD).

This observational study is the first to assess the prevalence of LTFU in children and adolescents with chronic endocrine diseases. LTFU was estimated at 14% in this well-characterized cohort of children followed at a single center. LTFU was strongly associated with higher age at diagnosis and with diagnosis before, as opposed to after, 2006. Unsurprisingly, the probability of LTFU was higher for patients with a lower frequency of medical visits and for those with a lower socioeconomic status, as reflected by their type of health insurance. The risk of LTFU was higher in patients with IGHD than in patients with other chronic endocrine disorders affecting growth and/or development.

Research priorities for chronic conditions affecting children have been identified in a wide range of areas within healthcare. Treatment adherence, access to healthcare, knowledge and self-management, and the transition to adult care are among the most frequently studied topics, with much less attention paid to the attendance of the patients and their families at clinic visits, lack of regular medical follow-up visits, and follow-up or LTFU [21]. Previous studies have reported rates of LTFU ranging from 24 to 47% in cohorts of pediatric patients followed for cancer, congenital heart disease, bladder exstrophy, celiac disease, or HIV seroconversion [8-12]. The definition of LTFU varies considerably between studies, ranging from 2 to 24 months without medical supervision, and the continuity of care, particularly in poor, rural areas, and the prevalence of LTFU and nonadherence to medical treatment depend largely on access to medical care and/or medical insurance coverage, particularly in low- and middle-income countries, whereas care is universal in France, even for patients covered by the special regimes for the underprivileged [22].

In our study, later diagnosis may reflect the parents’ perceptions of their child’s health or illness and their fears of the consequences of an unwanted diagnosis, as highlighted in the views of healthcare professionals concerning pediatric outpatient nonattendance [23].

The efficiency of therapeutic education programs for parents and patients and the potential of these programs to improve healthcare adherence and management in children and adolescents have been widely demonstrated [24, 25], but therapeutic compliance studies performed before 2000 showed that only 50% of patients with chronic illness followed their treatment correctly. The rate of treatment adherence is similar in adolescents and adults [16]. It has recently been shown that adolescents and young adults with chronic childhood-onset conditions have mortality rates up to 10 times higher than those without long-term disease [26]. Appropriate involvement of the parents and patients and the promotion of health self-efficacy, with the provision of relevant information at every stage and the teaching of management skills, are key features associated with better outcomes [27]. Significant improvements were made to our expert endocrine clinic in 2006, through the implementation of a therapeutic education program made possible by funding from the rare disease reference center plan implemented in France since 2005, potentially accounting for the lower risk of LTFU at our institution after 2006 (https://solidarites-sante.gouv.fr/soins-et-maladies/prises-en-charge-specialisees/maladies-rares/article/les-maladies-rares).

The failure of patients to attend clinics regularly is a known major problem. Previous studies, mostly focusing on adults [28] or the transition period [6, 28-30], have shown that the reasons for nonattendance vary with age, sex, socioeconomic status, and medical specialty [27-29, 31]. The motivations of the parents and patients and social barriers should also be taken into account [16, 32]. Despite the objective of free and universal access to care in France [20], our results indicate that lower socioeconomic status significantly increases the risk of LTFU in pediatric patients.

LTFU was more frequent in patients followed for IGHD than in those with other conditions. In these patients, LTFU mostly occurred at adolescence, or during or after puberty, with a median age at last visit of 14.7 years, as shown in other studies [13, 33]. Patients often stop attending clinic visits during GH treatment, before reaching their adult height. LTFU was also more likely in patients with idiopathic 46,XY DSD than in patients with other conditions, with a median age at last visit of 13.8 years [14]. LTFU at a key time for the physical and psychosocial development of the individual can be explained by the fact that the sudden stopping of the substitution treatment (i.e., growth hormone, sex steroids, or gonadotropins) does not lead to any immediate clinical manifestations. However, treatment at this crucial period of the patient’s life may have a determinant effect on future health, in terms of sexual maturation, the optimization of adult height and body composition, including the acquisition of bone mass, the prevention of metabolic syndrome, fertility, and quality of life [34]. By contrast, we found that patients with congenital adrenal insufficiency, in whom vigilant continuity of treatment is essential to avoid life-threatening emergencies [35], had a lower risk of LTFU.

One of the major strengths of this study is that all the patients in a defined population for whom comprehensive data were prospectively collected at diagnosis at a single pediatric endocrinology clinical center were included, making it possible to evaluate several demographic and clinical characteristics. The main limitation of this study is the observational nature of the retrospective data collection during follow-up. Furthermore, it was not possible to control for the effects of sex, cultural dimensions or family composition, family support, psychological aspects, disease perception, quality of the interactions between the patient and the doctor and careers, or the quality of therapeutic education [16]. Our logistic regression analysis provided no evidence for the utility of follow-up duration as a predictor of LTFU, but the patients with appropriate follow-up were younger than those in the LTFU group at the last visit, with median ages of 11.7 vs. 14.1 years, respectively. We cannot rule out the possibility that a certain number of the patients in the appropriate follow-up group will be lost to follow-up in the future, particularly when they reach adolescence, as already reported for children and adolescents with HIV infection [36]. However, the comprehensive data collection in this study made it possible to estimate several important explanatory variables simultaneously and to use all observations in the estimation process.

In conclusion, these original findings have important clinical implications for patient management, as they highlight the need for appropriate careful monitoring for the early recognition of features associated with a risk of LTFU in patients with chronic endocrine disorders of childhood onset, potentially improving their long-term outcomes. Future studies should explore target interventions for improving adherence to medical care and improvements in healthcare organization during the pediatric period.

The study protocol was approved by the Ethics Review Committee for Biomedical Research Projects Robert Debré University Hospital (No. 2017-342). Informed consent was obtained from the parents.

The authors have no conflicts of interest to declare.

This study was supported in part by the French Ministry of Health (Rare Disease Plan). Data collection, analysis and interpretation, and the decision to submit the paper for publication were the responsibility of the authors alone. The funding sources had no role in the study design, data collection, data interpretation, data analysis, or the writing of the report.

Dr. Laura Atger-Lallier designed the data collection instruments, collected data, carried out the initial analyses, drafted the initial manuscript, and reviewed and revised the manuscript. Prof. Juliane Léger conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. Dr. Sophie Guilmin-Crepon and Ms. Priscilla Boizeau carried out statistical analyses, and reviewed and revised the manuscript. Drs. Delphine Zenaty, Dominique Simon, Anne Paulsen, Laetitia Martinerie, Caroline Storey, and Prof. Jean-Claude Carel contributed to design of the study, analysis and interpretation of data, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

1.
Perrin
JM
,
Bloom
SR
,
Gortmaker
SL
.
The increase of childhood chronic conditions in the United States
.
JAMA
.
2007
Jun
;
297
(
24
):
2755
9
.
[PubMed]
0098-7484
2.
Blackwell
CK
,
Elliott
AJ
,
Ganiban
J
,
Herbstman
J
,
Hunt
K
,
Forrest
CB
, et al;
program collaborators for Environmental influences on Child Health Outcomes
.
General Health and Life Satisfaction in Children With Chronic Illness
.
Pediatrics
.
2019
Jun
;
143
(
6
):
e20182988
.
[PubMed]
0031-4005
3.
Kapellen
TM
,
Kiess
W
.
Transition of adolescents and young adults with endocrine diseases to adult health care
.
Best Pract Res Clin Endocrinol Metab
.
2015
Jun
;
29
(
3
):
505
13
.
[PubMed]
1521-690X
4.
Suris
JC
,
Akre
C
.
Key elements for, and indicators of, a successful transition: an international Delphi study
.
J Adolesc Health
.
2015
Jun
;
56
(
6
):
612
8
.
[PubMed]
1054-139X
5.
Rachas
A
,
Lefeuvre
D
,
Meyer
L
,
Faye
A
,
Mahlaoui
N
,
de La Rochebrochard
E
, et al
Evaluating Continuity During Transfer to Adult Care: A Systematic Review
.
Pediatrics
.
2016
Jul
;
138
(
1
):
e20160256
.
[PubMed]
0031-4005
6.
Campbell
F
,
Biggs
K
,
Aldiss
SK
,
O’Neill
PM
,
Clowes
M
,
McDonagh
J
, et al
Transition of care for adolescents from paediatric services to adult health services
.
Cochrane Database Syst Rev
.
2016
Apr
;
4
:
CD009794
.
[PubMed]
1469-493X
7.
Mazur
A
,
Dembinski
L
,
Schrier
L
,
Hadjipanayis
A
,
Michaud
PA
.
European Academy of Paediatric consensus statement on successful transition from paediatric to adult care for adolescents with chronic conditions
.
Acta Paediatr
.
2017
Aug
;
106
(
8
):
1354
7
.
[PubMed]
0803-5253
8.
Edgar
AB
,
Borthwick
S
,
Duffin
K
,
Marciniak-Stepak
P
,
Wallace
WHB
.
Survivors of childhood cancer lost to follow-up can be re-engaged into active long-term follow-up by a postal health questionnaire intervention.
Eur J Cancer Oxf Engl
1990
. 2012 May;48(7):1066–73.
9.
Mackie
AS
,
Ionescu-Ittu
R
,
Therrien
J
,
Pilote
L
,
Abrahamowicz
M
,
Marelli
AJ
.
Children and adults with congenital heart disease lost to follow-up: who and when?
Circulation
.
2009
Jul
;
120
(
4
):
302
9
.
[PubMed]
0009-7322
10.
Kariminia
A
,
Law
M
,
Davies
MA
,
Vinikoor
M
,
Wools-Kaloustian
K
,
Leroy
V
, et al
Mortality and losses to follow-up among adolescents living with HIV in the IeDEA global cohort collaboration. J Int AIDS Soc. 2018 Dec;21(12):e25215. Haddad E, Sancaktutar AA, Palmer BW, Aston C, Kropp BP. Who, where, and why are patients lost to follow-up? A 20-year study of bladder exstrophy patients at a single institution
.
J Pediatr Urol
.
2018
;
14
(
3
):
276.e1
6
.1477-5131
11.
Haddad E, Sancaktutar AA, Palmer BW, Aston C, Kropp BP. Who, where, and why are patients lost to follow-up? A 20-year study of bladder exstrophy patients at a single institution. J Pediatr Urol. 2018;14(3):276.e1–6.
12.
Mozer-Glassberg
Y
,
Zevit
N
,
Rosenbach
Y
,
Hartman
C
,
Morgenstern
S
,
Shamir
R
.
Follow-up of children with celiac disease - lost in translation?
Digestion
.
2011
;
83
(
4
):
283
7
.
[PubMed]
0012-2823
13.
Carel
JC
,
Ecosse
E
,
Nicolino
M
,
Tauber
M
,
Leger
J
,
Cabrol
S
, et al
Adult height after long term treatment with recombinant growth hormone for idiopathic isolated growth hormone deficiency: observational follow up study of the French population based registry
.
BMJ
.
2002
Jul
;
325
(
7355
):
70
.
[PubMed]
0959-8138
14.
Blanc
T
,
Ayedi
A
,
El-Ghoneimi
A
,
Abdoul
H
,
Aigrain
Y
,
Paris
F
, et al
Testicular function and physical outcome in young adult males diagnosed with idiopathic 46 XY disorders of sex development during childhood
.
Eur J Endocrinol
.
2011
Dec
;
165
(
6
):
907
15
.
[PubMed]
0804-4643
15.
Graves
MM
,
Roberts
MC
,
Rapoff
M
,
Boyer
A
.
The efficacy of adherence interventions for chronically ill children: a meta-analytic review
.
J Pediatr Psychol
.
2010
May
;
35
(
4
):
368
82
.
[PubMed]
0146-8693
16.
KyngAs HA
.
Kroll T, Duffy ME. Compliance in adolescents with chronic diseases: a review
.
J Adolesc Health Off Publ Soc Adolesc Med.
2000
Jun
;
26
(
6
):
379
88
.
17.
Clayton
PE
,
Cuneo
RC
,
Juul
A
,
Monson
JP
,
Shalet
SM
,
Tauber
M
;
European Society of Paediatric Endocrinology
.
Consensus statement on the management of the GH-treated adolescent in the transition to adult care
.
Eur J Endocrinol
.
2005
Feb
;
152
(
2
):
165
70
.
[PubMed]
0804-4643
18.
Saba
C
,
Guilmin-Crepon
S
,
Zénaty
D
,
Martinerie
L
,
Paulsen
A
,
Simon
D
, et al
Early Determinants of Thyroid Function Outcomes in Children with Congenital Hypothyroidism and a Normally Located Thyroid Gland: A Regional Cohort Study
.
Thyroid
.
2018
Aug
;
28
(
8
):
959
67
.
[PubMed]
1050-7256
19.
Léger
J
,
Carel
JC
.
MANAGEMENT OF ENDOCRINE DISEASE: arguments for the prolonged use of antithyroid drugs in children with Graves’ disease
.
Eur J Endocrinol
.
2017
Aug
;
177
(
2
):
R59
67
.
[PubMed]
0804-4643
20.
Horton
R
,
Ceschia
A
.
France: a philosophy for health
.
Lancet
.
2016
May
;
387
(
10034
):
2174
6
.
[PubMed]
0140-6736
21.
Odgers
HL
,
Tong
A
,
Lopez-Vargas
P
,
Davidson
A
,
Jaffe
A
,
McKenzie
A
, et al
Research priority setting in childhood chronic disease: a systematic review
.
Arch Dis Child
.
2018
Oct
;
103
(
10
):
942
51
.
[PubMed]
0003-9888
22.
Alizadeh
F
,
Mfitumuhoza
G
,
Stephens
J
,
Habimaana
C
,
Myles
K
,
Baganizi
M
, et al
Identifying and Reengaging Patients Lost to Follow-Up in Rural Africa: The “Horizontal” Hospital-Based Approach in Uganda. Glob Health Sci Pract.
2019
22;7(1):103–15.
23.
Cameron
E
,
Heath
G
,
Redwood
S
,
Greenfield
S
,
Cummins
C
,
Kelly
D
, et al
Health care professionals’ views of paediatric outpatient non-attendance: implications for general practice
.
Fam Pract
.
2014
Feb
;
31
(
1
):
111
7
.
[PubMed]
0263-2136
24.
Adams
JS
,
Woods
ER
.
Redesign of chronic illness care in children and adolescents: evidence for the chronic care model
.
Curr Opin Pediatr
.
2016
Aug
;
28
(
4
):
428
33
.
[PubMed]
1040-8703
25.
Ha Dinh
TT
,
Bonner
A
,
Clark
R
,
Ramsbotham
J
,
Hines
S
.
The effectiveness of the teach-back method on adherence and self-management in health education for people with chronic disease: a systematic review
.
JBI Database Syst Rev Implement Reports
.
2016
Jan
;
14
(
1
):
210
47
.
[PubMed]
2202-4433
26.
Rachas
A
,
Tuppin
P
,
Meyer
L
,
Falissard
B
,
Faye
A
,
Mahlaoui
N
, et al
Excess mortality and hospitalizations in transitional-age youths with a long-term disease: A national population-based cohort study
.
PLoS One
.
2018
Mar
;
13
(
3
):
e0193729
.
[PubMed]
1932-6203
27.
Colver
A
,
McConachie
H
,
Le Couteur
A
,
Dovey-Pearce
G
,
Mann
KD
,
McDonagh
JE
, et al
A longitudinal, observational study of the features of transitional healthcare associated with better outcomes for young people with long-term conditions.
BMC Med.
2018
23;16(1):111.
28.
Bachelot
A
,
Vialon
M
,
Baptiste
A
,
Tejedor
I
,
Elie
C
,
Polak
M
, et al
Impact of transition on quality of life in patients with congenital adrenal hyperplasia diagnosed during childhood
.
Endocr Connect
.
2017
Aug
;
6
(
7
):
422
9
.
[PubMed]
2049-3614
29.
White
M
,
O’Connell
MA
,
Cameron
FJ
.
Transition to adult endocrine services: what is achievable? The diabetes perspective
.
Best Pract Res Clin Endocrinol Metab
.
2015
Jun
;
29
(
3
):
497
504
.
[PubMed]
1521-690X
30.
Gleeson
H
,
Turner
G
.
Transition to adult services
.
Arch Dis Child Educ Pract Ed
.
2012
Jun
;
97
(
3
):
86
92
.
[PubMed]
1743-0585
31.
Sokol
R
,
Austin
A
,
Chandler
C
,
Byrum
E
,
Bousquette
J
,
Lancaster
C
, et al
Screening Children for Social Determinants of Health: A Systematic Review
.
Pediatrics
.
2019
Oct
;
144
(
4
):
e20191622
.
[PubMed]
0031-4005
32.
Sawyer
SM
,
Afifi
RA
,
Bearinger
LH
,
Blakemore
SJ
,
Dick
B
,
Ezeh
AC
, et al
Adolescence: a foundation for future health
.
Lancet
.
2012
Apr
;
379
(
9826
):
1630
40
.
[PubMed]
0140-6736
33.
Gelwane
G
,
Garel
C
,
Chevenne
D
,
Armoogum
P
,
Simon
D
,
Czernichow
P
, et al
Subnormal serum insulin-like growth factor-I levels in young adults with childhood-onset nonacquired growth hormone (GH) deficiency who recover normal gh secretion may indicate less severe but persistent pituitary failure
.
J Clin Endocrinol Metab
.
2007
Oct
;
92
(
10
):
3788
95
.
[PubMed]
0021-972X
34.
Hokken-Koelega
A
,
van der Lely
AJ
,
Hauffa
B
,
Häusler
G
,
Johannsson
G
,
Maghnie
M
, et al
Bridging the gap: metabolic and endocrine care of patients during transition
.
Endocr Connect
.
2016
Nov
;
5
(
6
):
R44
54
.
[PubMed]
2049-3614
35.
Eyal
O
,
Levin
Y
,
Oren
A
,
Zung
A
,
Rachmiel
M
,
Landau
Z
, et al
Adrenal crises in children with adrenal insufficiency: epidemiology and risk factors
.
Eur J Pediatr
.
2019
May
;
178
(
5
):
731
8
.
[PubMed]
0340-6199
36.
Kranzer
K
,
Bradley
J
,
Musaazi
J
,
Nyathi
M
,
Gunguwo
H
,
Ndebele
W
, et al
Loss to follow-up among children and adolescents growing up with HIV infection: age really matters. J Int AIDS Soc.
2017
17;20(1):21737.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.