Duchenne muscular dystrophy is a devastating neuromuscular disorder characterized by the loss of dystrophin, inevitably leading to cardiomyopathy. Despite publications on prophylaxis and treatment with cardiac medications to mitigate cardiomyopathy progression, gaps remain in the specifics of medication initiation and optimization.

This document is an expert opinion statement, addressing a critical gap in cardiac care for Duchenne muscular dystrophy. It provides thorough recommendations for the initiation and titration of cardiac medications based on disease progression and patient response. Recommendations are derived from the expertise of the Advance Cardiac Therapies Improving Outcomes Network and are informed by established guidelines from the American Heart Association, American College of Cardiology, and Duchenne Muscular Dystrophy Care Considerations. These expert-derived recommendations aim to navigate the complexities of Duchenne muscular dystrophy-related cardiac care.

Comprehensive recommendations for initiation, titration, and optimization of critical cardiac medications are provided to address Duchenne muscular dystrophy-associated cardiomyopathy.

The management of Duchenne muscular dystrophy requires a multidisciplinary approach. However, the diversity of healthcare providers involved in Duchenne muscular dystrophy can result in variations in cardiac care, complicating treatment standardization and patient outcomes. The aim of this report is to provide a roadmap for managing Duchenne muscular dystrophy-associated cardiomyopathy, by elucidating timing and dosage nuances crucial for optimal therapeutic efficacy, ultimately improving cardiac outcomes, and improving the quality of life for individuals with Duchenne muscular dystrophy.

This document seeks to establish a standardized framework for cardiac care in Duchenne muscular dystrophy, aiming to improve cardiac prognosis.

Attention Deficit / Hyperactivity Disorder (ADHD) is a highly prevalent neurodevelopmental condition characterized by inattention, motor hyperactivity and impulsivity. ADHD cognitive and behavioral presentation is characterized by a high heterogeneity (APA, 2013). Indeed, a complex diagnostic process, that considers several validated tools, is, to date, necessary.

The main aim is to develop supervised machine learning (ML) algorithms that could be used to support the diagnostic process for ADHD, by identifying the most relevant features in discriminating between the presence or absence of the ADHD diagnosis in children.

We analyzed data from 342 children (Mean age: 8y 8m ± 1y; 61 F) referred for possible ADHD symptomatology. Assessments were performed by an expert clinician and through questionnaires: Social Responsiveness Scale (SRS), Child Behavior Checklist (CBCL), Conners Rating Scale for Parents (CPRS) and for Teachers (CTRS). Data were analyzed using a decision tree classifier and random forest algorithms.

The decision tree model performed an accuracy of 0.71. The random forest model that was identified as the best tested, performed an accuracy of 0.77 (Figure 1) and it identified as most informative parent- and teacher-rated DSM-oriented ADHD symptoms (Figure 2).

Figure 1: Random forest confusion matrix and statistics.

Figure 2: Ranking of variables importance.

A random forest classifier could represent an effective algorithm to support the identification of ADHD children and to simplify the diagnostic process as an initial step. The use of supervised machine learning algorithms could be useful in helping the diagnostic process, highlighting the importance of a personalized medicine approach.

No significant relationships.

Hepatic ones are some of the most described somatic complications in anorexia nervosa (AN) affected patients. They can be due to malnutrition, which is the more usual thing, or due to re-feeding. The first one can lead to more marked elevations of the hepatic enzymes, especially alanine-aminotransferase (ALT). It’s been also described the relation between a sharply decreased body mass index (BMI) and this kind of complications, but there are still to determine more predictors.

Identifying clinical predictors of hepatic complications in AN.

We analysed data from 71 AN affected patients hospitalized at Bellvitge Hospital from January 2016 to October 2021. We used IBM SPSS Statistics 22 to do all the statistics in this work.

The medium age of the sample was 27.66 years with 10.8 years of evolution of AN. The medium BMI was 13.88. 33.80% of them had some sort of hepatic enzymes elevation, two of them a several one. AST, ALT and ALP were significantly more elevated in those patients with lower BMI. GGT was significantly more elevated in patients with more years of disorder development. We didn’t identify correlation between any purgative method and hepatic alterations.

The elevation of ALT, AST and ALP seems to be related with the BMI of the patients, while the elevation of the GGT turns out to be related to the time of evolution of the eating disorder. Purgative methods don’t seem to be related to the development of hepatic alterations in AN.

No significant relationships.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by lack of self-regulation and deficits in organizing behaviors in response to emotional stimuli. Methylphenidate (MPH) is one of the most effective psychostimulant drugs for ADHD, however, a possible predictive utility of brain hemodynamic data related to MPH administration and its relation to clinical symptomatology is still not clear. To address these questions, we used Near Infrared Spectroscopy (NIRS) technology, a non-invasive optical technique that allows to investigate the effect of psychopharmacological treatment on cortical hemodynamics.

Twenty children with ADHD underwent a three-waves study and 25 healthy controls were recruited at W1. At W2 children with ADHD received first MPH administration and at W3 they reached the titration phase. At each phase children performed - during NIRS recording - an emotional continuous performance task with visual stimuli of different emotional content. Clinical data were also collected at W1 and W3. We investigated the relationship among the difference between NIRS activation at W2 and W1 (Delta1) and W3 and W2 (Delta2), for each subject, task condition and brain region. Lastly, we investigated correlations between the Delta1 and clinical symptomatology indexes at W1 and between Delta2 and clinical data at W3.

Our study results suggest that hemodynamic changes in right prefrontal region probably induced by first MPH administration could predict hemodynamic changes related to MPH titration phase. These biological indexes could be associated to clinical evidences related not only to core ADHD symptoms but also to affective correlates.

No significant relationships.

Epigenetics hypothesizes a crucial link between postnatal risk factors, individual response to stress, DNA methylation and psychiatric symptomatology changes during life.

We analyzed methylation within two gene exons: NR3C1 and SLC6A4, which are involved in responses to environmental stressors. We investigated the relationship between methylation, postnatal risk factors and psychopathology assessed by Child Behavior Checklist (CBCL) in our help-seeking sample evaluated in infancy (W1), preadolescence (W2) and adult life (W3).

Postnatal risk factors data were collected at W1 in 205 clinical subjects (156 M, 49 F; age=9,13±1,95). The CBCL scores were collected at W1 and W2 (W2 age=14,52±2,12). Data regarding methylation were collected at W2. At W3 we are also collecting clinical scores. A Spearman correlation coefficient was calculated between methylation percentage and clinical data at W2. The externalizing and internalizing trajectories were evaluated through repeated measure ANOVA with postnatal risk factors (presence/absence) as between-groups factor.

Significant associations were found between methylation and internalizing and total clinical scores (Table 1). The rm-ANOVA results showed a significant interaction between the CBCL internalizing score and presence/absence of postnatal risk, with higher internalizing problems in subjects that were exposed to postnatal risk factors. This effect was significant at W2 but not at W1 (Figure 1).

Psychopathological symptoms trajectories could depend on epigenetics and early environmental risk factors. Further analyses will address a Linear Discriminant Analysis to proceed to a machine learning oriented approach.

No significant relationships.

Our 15-years follow-up ReMIND project aims to re-assess an epidemiological and a clinical sample of adults (Wave 3), who were assessed in preadolescence (Wave 1) and adolescence (Wave 2), to evaluate symptoms trajectories and their relationship with genetic/epigenetic data, environmental risk factors and neuroimaging measures.

Here, we depict preliminary results regarding the epidemiological sample.

We assessed internalizing and externalizing symptoms in 40 italian subjects (25 F) from general population at three waves (W1 mean age: 12±0,82; W2 mean age: 17±0,88, W3 mean age: 28±1), through the Child Behavior Checklist (W1 and W2) or the Adult Self Report (W3), and perinatal risk factors through a socio-anamnestic questionnaire, by a new online platform (MedicalBit). We analyzed symptoms trajectories and their relation with perinatal risk factors through a repeated measures multivariate analysis of variance (rm-MANOVA).

rm-MANOVA results show that high number of perinatal risks was significantly associated with higher internalizing symptomatology in preadolescence but not in adolescence and adult life. The mean difference was 8 T-points. The same trend is evident in adolescence but not in adult age (Graph 1). Perinatal risk factors did not have a significant effect on externalizing symptoms at any time point, despite a non-significant trend is evident (Graph 2).

Our preliminary results suggest a trend of increased internalizing symptoms from childhood to adulthood and a significant role of perinatal risk factors in pre-adolescence. Further investigations are necessary to better understand symptoms trajectories and the role of biological and environmental factors.

No significant relationships.

Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys.

The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women.

Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs.

Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.

A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders.

In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18–100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction.

An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6–17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both.

CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.

Research on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. Results are inconsistent about pre-trauma predictors.

The WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD.

20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low [odds-ratio (OR) 0.2–0.3] early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66–55% v. 43%) and later-recovery (75–68% v. 39%).

We found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.

Although specific phobia is highly prevalent, associated with impairment, and an important risk factor for the development of other mental disorders, cross-national epidemiological data are scarce, especially from low- and middle-income countries. This paper presents epidemiological data from 22 low-, lower-middle-, upper-middle- and high-income countries.

Data came from 25 representative population-based surveys conducted in 22 countries (2001–2011) as part of the World Health Organization World Mental Health Surveys initiative (n = 124 902). The presence of specific phobia as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition was evaluated using the World Health Organization Composite International Diagnostic Interview.

The cross-national lifetime and 12-month prevalence rates of specific phobia were, respectively, 7.4% and 5.5%, being higher in females (9.8 and 7.7%) than in males (4.9% and 3.3%) and higher in high- and higher-middle-income countries than in low-/lower-middle-income countries. The median age of onset was young (8 years). Of the 12-month patients, 18.7% reported severe role impairment (13.3–21.9% across income groups) and 23.1% reported any treatment (9.6–30.1% across income groups). Lifetime co-morbidity was observed in 60.5% of those with lifetime specific phobia, with the onset of specific phobia preceding the other disorder in most cases (72.6%). Interestingly, rates of impairment, treatment use and co-morbidity increased with the number of fear subtypes.

Specific phobia is common and associated with impairment in a considerable percentage of cases. Importantly, specific phobia often precedes the onset of other mental disorders, making it a possible early-life indicator of psychopathology vulnerability.

Research on post-traumatic stress disorder (PTSD) following natural and human-made disasters has been undertaken for more than three decades. Although PTSD prevalence estimates vary widely, most are in the 20–40% range in disaster-focused studies but considerably lower (3–5%) in the few general population epidemiological surveys that evaluated disaster-related PTSD as part of a broader clinical assessment. The World Mental Health (WMH) Surveys provide an opportunity to examine disaster-related PTSD in representative general population surveys across a much wider range of sites than in previous studies.

Although disaster-related PTSD was evaluated in 18 WMH surveys, only six in high-income countries had enough respondents for a risk factor analysis. Predictors considered were socio-demographics, disaster characteristics, and pre-disaster vulnerability factors (childhood family adversities, prior traumatic experiences, and prior mental disorders).

Disaster-related PTSD prevalence was 0.0–3.8% among adult (ages 18+) WMH respondents and was significantly related to high education, serious injury or death of someone close, forced displacement from home, and pre-existing vulnerabilities (prior childhood family adversities, other traumas, and mental disorders). Of PTSD cases 44.5% were among the 5% of respondents classified by the model as having highest PTSD risk.

Disaster-related PTSD is uncommon in high-income WMH countries. Risk factors are consistent with prior research: severity of exposure, history of prior stress exposure, and pre-existing mental disorders. The high concentration of PTSD among respondents with high predicted risk in our model supports the focus of screening assessments that identify disaster survivors most in need of preventive interventions.

Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs.

General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure.

Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types – witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury – accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events.

Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.

To examine cross-national patterns and correlates of lifetime and 12-month comorbid DSM-IV anxiety disorders among people with lifetime and 12-month DSM-IV major depressive disorder (MDD).

Nationally or regionally representative epidemiological interviews were administered to 74 045 adults in 27 surveys across 24 countries in the WHO World Mental Health (WMH) Surveys. DSM-IV MDD, a wide range of comorbid DSM-IV anxiety disorders, and a number of correlates were assessed with the WHO Composite International Diagnostic Interview (CIDI).

45.7% of respondents with lifetime MDD (32.0–46.5% inter-quartile range (IQR) across surveys) had one of more lifetime anxiety disorders. A slightly higher proportion of respondents with 12-month MDD had lifetime anxiety disorders (51.7%, 37.8–54.0% IQR) and only slightly lower proportions of respondents with 12-month MDD had 12-month anxiety disorders (41.6%, 29.9–47.2% IQR). Two-thirds (68%) of respondents with lifetime comorbid anxiety disorders and MDD reported an earlier age-of-onset (AOO) of their first anxiety disorder than their MDD, while 13.5% reported an earlier AOO of MDD and the remaining 18.5% reported the same AOO of both disorders. Women and previously married people had consistently elevated rates of lifetime and 12-month MDD as well as comorbid anxiety disorders. Consistently higher proportions of respondents with 12-month anxious than non-anxious MDD reported severe role impairment (64.4 v. 46.0%; χ21 = 187.0, p < 0.001) and suicide ideation (19.5 v. 8.9%; χ21 = 71.6, p < 0.001). Significantly more respondents with 12-month anxious than non-anxious MDD received treatment for their depression in the 12 months before interview, but this difference was more pronounced in high-income countries (68.8 v. 45.4%; χ21 = 108.8, p < 0.001) than low/middle-income countries (30.3 v. 20.6%; χ21 = 11.7, p < 0.001).

Patterns and correlates of comorbid DSM-IV anxiety disorders among people with DSM-IV MDD are similar across WMH countries. The narrow IQR of the proportion of respondents with temporally prior AOO of anxiety disorders than comorbid MDD (69.6–74.7%) is especially noteworthy. However, the fact that these proportions are not higher among respondents with 12-month than lifetime comorbidity means that temporal priority between lifetime anxiety disorders and MDD is not related to MDD persistence among people with anxious MDD. This, in turn, raises complex questions about the relative importance of temporally primary anxiety disorders as risk markers v. causal risk factors for subsequent MDD onset and persistence, including the possibility that anxiety disorders might primarily be risk markers for MDD onset and causal risk factors for MDD persistence.