Ten Years (2011–2021) of the Italian Lombardy ADHD Register for the Diagnosis and Treatment of Children and Adolescents with ADHD

Background: The purpose of this article is to update the diagnostic assessment, therapeutic approach, and 12–18 month follow-up of patients added to the Italian Lombardy Attention Deficit Hyperactivity Disorder (ADHD) Register. Methods: Medical records of patients added to the Registry from 2011 to 2021 were analysed. Results: 4091 of 5934 patients met the criteria for a diagnosis of ADHD, and 20.3% of them presented a familiarity with the disorder. A total of 2879 children (70.4%) had at least one comorbidity disorder, in prevalence a learning disorder (39%). Nearly all (95.9%) received at least one psychological prescription, 17.9% of them almost one pharmacological treatment, and 15.6% a combination of both. Values of ≥5 of the Clinical Global Impression—Severity scale (CGI-S) are more commonly presented by patients with a pharmacological prescription than with a psychological treatment (p < 0.0001). A significant improvement was reported in half of the patients followed after 1 year, with Clinical Global Impression—Improvement scale (CGI-I) ≤ 3. In all, 233 of 4091 are 18-year-old patients. Conclusions: A ten-year systematic monitoring of models of care was a fruitful shared and collaborative initiative in order to promote significant improvement in clinical practice, providing effective and continuous quality of care. The unique experience reported here should spread.


Introduction
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects 5.9% of children and persists into adulthood for two-thirds of them [1,2], with great impairments in academic achievement and work [3]. The core symptoms are inattention, restlessness and impulsivity, which are more frequent in boys than girls (ratio 3:1). In Italy, the prevalence of the disorder ranges from 1.1 to 3.1% of the paediatric population, considering only subjects with a diagnosis confirmed by clinical evaluation [4].
The wide variability depends on the different diagnostic procedures adopted to assess children and the criteria used, and the period of time over which assessment is conducted [5]. The peak age of diagnosis of ADHD is in primary school children aged 5-10 years [6], and children born later in the school year are more likely to receive an ADHD diagnosis than their same school-year peers [7]. According to the national and international guidelines [8,9], the diagnosis of ADHD is based on a careful and systematic assessment of a lifetime history of symptoms, childhood onset, and impairment in some contexts (schools, relationships, home) [10]. Information about the medical history of psychiatric and neurological problems is also important. Psychiatric comorbidity is thus a

Materials and Methods
A retrospective study based on medical records was conducted. Data were identified from the Regional ADHD Registry. Formal ethical review board approval was not required for the present updating because it was previously approved by the Institutional Review Board of the Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. Written informed consent was obtained from all patients before data collection. We used the previously described methodology and reported data concerning the local health setting [7], the characteristics of the ADHD Registry activated in Lombardy in June 2011 [20,21], the systematic work carried out by the 18 ADHD centres [19], and the diagnostic assessment and the treatment conducted by all involved clinicians, according to the national and international guidelines [8,9]. Behavioural and emotional problems were highlighted with the most used and validated rating scales for parents and teachers, Conners' Parent Rating Scale (CPRS) [22], Conners' Teacher Rating Scale (CTRS) [23], and the Child Behaviour Checklist (CBCL) [24], while symptom severity and symptom improvement were quantified, respectively, with the use of the Clinical Global Impression-Severity scale and the Clinical Global Impressions-Improvement scale [25]. Results from the scales were analysed and compared with the perceptions of parents and teachers, as well as the perceptions of mothers and fathers. The Clinical Global Impressions-Improvement Scale scores were analysed after 12-18 months of follow-up. The percentages of completeness of the seven areas of the shared diagnostic assessment (Clinical Interview, Neurological Examination, IQ Evaluation, Diagnostic Interview, Parents and Teachers Assessment, Clinical Severity Evaluation) of all regional centres were analysed and displayed on radar chart axes with a range of 0 to 100% Data were extracted from the database and analyses were updated on 1 April 2021, and data referred to patients added between 2011 and 2021.

Data Analyses
All data were entered in an SAS/STAT database (SAS Version 9, SAS Institute, Inc., Cary, NC, USA). Descriptive statistics were computed for the entire study population and for subgroups. The Wilcoxon test was used to compare continuous variables, whereas chi-square tests were used to compare categorical variables. V-Cramer and Wilcoxon effect sizes were calculated (Supplementary Materials). Both values vary from 0 to 1; the closer the value was to 1, the stronger the significant difference between the categorical and the continuous variables was. A multivariate logistic regression analysis with stepwise selection was also carried out to assess the determinants of disease and treatment. Moreover, interrater agreement (parents vs. teachers; mothers vs. fathers) on symptom scores for each diagnostic scale was established by Kappa coefficient of agreement (K). The results are presented as the number, frequency (%), and mean or median; p < 0.05 was considered to be significant.

Results
A total of 7053 children were added to the registry from June 2011 to December 2021, of whom 6188 were children and adolescents accessing the ADHD centres for the first time (range 89-1010 patients per centre, median = 248) for suspected ADHD diagnosis. Most of the patients (5934) had completed the diagnostic assessment (Table 1). Children had a median age of 9 years (range 7-11); most of them were males (4960 (83.6%)) and 974 (16.4%) were females. In all, 4091 patients received a diagnosis of ADHD based on the Diagnostic and Statistical Manual of Mental Disorders [26] criteria, 3484 (85.2%) of whom were males and 607 (14.8%) females. The cumulative incidence of ADHD in the 2011 and 2021 period was valued to be 0.26% (95% confidence interval (CI = [0.94-1.24]) of the resident population of the same age range, with a spike at 8 years of age ( Figure 1).
The percentages of completeness of the seven areas of the shared diagnostic assessment (Clinical Interview, Neurological Examination, IQ Evaluation, Diagnostic Interview, Parents and Teachers Assessment, Clinical Severity Evaluation) of all regional centres were analysed and displayed on radar chart axes with a range of 0 to 100% Data were extracted from the database and analyses were updated on 1 April 2021, and data referred to patients added between 2011 and 2021.

Data Analyses
All data were entered in an SAS/STAT database (SAS Version 9, SAS Institute, Inc., Cary, NC, USA). Descriptive statistics were computed for the entire study population and for subgroups. The Wilcoxon test was used to compare continuous variables, whereas chisquare tests were used to compare categorical variables. V-Cramer and Wilcoxon effect sizes were calculated (Supplementary Materials). Both values vary from 0 to 1; the closer the value was to 1, the stronger the significant difference between the categorical and the continuous variables was. A multivariate logistic regression analysis with stepwise selection was also carried out to assess the determinants of disease and treatment. Moreover, interrater agreement (parents vs. teachers; mothers vs. fathers) on symptom scores for each diagnostic scale was established by Kappa coefficient of agreement (K). The results are presented as the number, frequency (%), and mean or median; p < 0.05 was considered to be significant.

Results
A total of 7053 children were added to the registry from June 2011 to December 2021, of whom 6188 were children and adolescents accessing the ADHD centres for the first time (range 89-1010 patients per centre, median = 248) for suspected ADHD diagnosis. Most of the patients (5934) had completed the diagnostic assessment (Table 1). Children had a median age of 9 years (range 7-11); most of them were males (4960 (83.6%)) and 974 (16.4%) were females. In all, 4091 patients received a diagnosis of ADHD based on the Diagnostic and Statistical Manual of Mental Disorders [26] criteria, 3484 (85.2%) of whom were males and 607 (14.8%) females. The cumulative incidence of ADHD in the 2011 and 2021 period was valued to be 0.26% (95% confidence interval (CI = [0.94-1.24]) of the resident population of the same age range, with a spike at 8 years of age ( Figure 1).  The characteristics strongly associated with ADHD were lower age, male gender, only child, not born in Italy, adopted, support teacher, lower educational level of parents, unemployed father, ADHD familiarity and psychiatric comorbidity ( were higher in patients without ADHD. The presence of a neurological condition was more frequent (n = 121, 2%). Table 1. Demographic characteristics of the ADHD patients.

Continuity of Care and Management
Throughout the regional database system, data on patient care from the first access to the diagnosis and data on treatment prescriptions and follow-up visits were systematically collected. As shown in Figure 2, the diagnostic evaluation was full and accurate: each axis has a range of 0 to 100% and represents one of the seven areas of the shared diagnostic assessment (Clinical Interview, Neurological Examination, IQ Evaluation, Diagnostic Interview, Parents and Teachers Assessment, Clinical Severity Evaluation), while the three datasets represent the performance scores of the most (average = 100%) and least compliant (average = 91.01%) ADHD centre, as well as the total completeness (average = 97.86%) estimated by the analysis of data recorded by all 18 ADHD centres. Overall, 320 of 4091 patients with a diagnosis of ADHD were discharged during the first 3 months; 1468 patients with ADHD had been monitored for more than 1 year after the diagnosis, half of whom had a significant improvement with CGI-I scores of 1-3, and the majority of these (89%) were in a stable condition with scores of 4 on the CGI-I. In all, 755 patients reached the legal age (range 18-27 years), 31.3% of whom just turned 18 years old. sessment (Clinical Interview, Neurological Examination, IQ Evaluation, Diagnostic Interview, Parents and Teachers Assessment, Clinical Severity Evaluation), while the three datasets represent the performance scores of the most (average = 100%) and least compliant (average = 91.01%) ADHD centre, as well as the total completeness (average = 97.86%) estimated by the analysis of data recorded by all 18 ADHD centres. Overall, 320 of 4091 patients with a diagnosis of ADHD were discharged during the first 3 months; 1468 patients with ADHD had been monitored for more than 1 year after the diagnosis, half of whom had a significant improvement with CGI-I scores of 1-3, and the majority of these (89%) were in a stable condition with scores of 4 on the CGI-I. In all, 755 patients reached the legal age (range 18-27 years), 31.3% of whom just turned 18 years old.

Discussion
Ten years after the creation of the Lombardy Registry Project, clinical and service assessment data revealed the effectiveness and usefulness of this regional project in providing assistance and continuity of care to ADHD patients and their families. Over the years, the registry was monitored to achieve clinical improvement, using systematic activities and an interactive system evaluation to test the change, according to the main clinical quality improvement features [27]. The clinical characteristics of the ADHD patients of the Lombardy Registry Project were in line with the literature; the peak age of diagnosis was in primary school children aged 5-10 years [6], and LD was the main psychiatric comorbidity followed by ODD, anxiety, and sleeping disorders [1,12]. The most associated chronic disease was a neurological condition. Concerning treatment, data extracted from the registry highlighted a relation between some clinical characteristics and the type of prescription at diagnosis; according to the literature, the symptom severity increased the likelihood of being prescribed ADHD medication [28]. The higher the CGI-S score, the higher the probability of receiving a medical prescription, in particular for patients with ODD, an intellectual disability, tics or a coordination disorder. Differently from what we expected, learning problems were not associated with being prescribed medication, suggesting that learning problems may not be pertinent to pharmacological treatment decisions for children with ADHD. Pharmacological prescription was infrequent (18%), and nearly all of the patients (96%) received a psychological prescription such as child, parent or teacher training. Comparing data with higher rates reported in other countries [29], in Italy child psychiatrists' professional attitude leaned more toward behavioural treatments than to the use of drugs [30]. In general, half of the patients with a diagnosis of ADHD and in treatment for almost one year (follow-up between 12 and 18 months) reported an improvement in their level of symptom severity on the CGI-I score. These data were comforting, suggesting the clinical care utility of a continuously monitored, standardised system. The project represents a great opportunity to improve collaboration, share assessment approaches and promote the continuity of care of patients affected by ADHD, monitoring their treatments and healthcare pathway. This represented an important value for the project; continuously monitoring and sharing data is an important approach in order to ensure the quality of care. The ADHD project could represent an example of a healthcare system for other chronic conditions and psychiatric disorders in childhood in order to promote the continuity and improvement of childcare. Particular attention should be paid to a particular phase called transition-the passage between child care to adult care; after ten years of the project, many children became adolescents, and some of them are near the boundary age. The transition process not only concerns healthcare but also involves the transition to adulthood, finding employment or continuing the education process; therefore, it is important for the adolescent to be prepared to manage their medical condition and pharmacological treatment. Once reaching adulthood, the risk is being discharged by the services and not receiving prescribed medication. In order to avoid this situation, it is very important to promote the continuity and monitoring of childcare. A great deal has been done, but a lot of work is still necessary for the best management of ADHD across the lifespan. The limit of the project's approach is that it represents a national uniqueness. Moreover, the registry, due to its nature of being an observatory of healthcare provided by a service (even if public), does not contemplate the rate of patients who interrupted the care pathway or who did not start it, failing to show up from the start. Despite the remarkable improvements made in the last twenty years for providing appropriate diagnostic and treatment services for children with ADHD, also as a result of the landmark Multimodal Treatment Study of Children with Attention Deficit/Hyperactivity Disorder (MTA) trial [31], practice is still different between and within countries. Recommendations and guidelines for ADHD management in children and adolescents were produced by several parties and individual centres adapted their care. The findings reported here are not different from others reported in the literature where health services and care are different. However, the heart of the Italian Lombardy ADHD Registry lies in the approach: collaborative, shared between and within the participating centres, over time. It is an unusual approach in the interest of the patients and carers.

Conclusions
The Regional ADHD Registry represents a distinctive tool, a unique experience in the international context, to help guarantee a shared pathway of care in ADHD children. Continuous, systematic monitoring allows resources to be invested appropriately, such as in promoting progressive and significant improvement in clinical practice, ensuring a shared and efficient quality of care. Training initiatives involving clinicians, patients, parents and teachers may be useful in order to raise awareness about the disorder in clinical practice.