Longterm outcomes in patients with acute and chronic myocardial injury

Background: Myocardial injury is defined as any cardiac troponin (cTn) level above the upper reference limit, namely, the 99th percentile value, and is caused by either ischemic or nonischemic events. The presence of acute myocardial injury (i.e., myocardial injury with a dynamic change in cTn levels) with evidence of myocardial ischemia is required for the diagnosis of myocardial infarction (MI). Nonischemic myocardial injury, defined as myocardial injury without evidence of ischemia, and type 2 MI are linked to a substantial risk of death and a poor prognosis. The purpose of this thesis was to study the characteristics, risks of death, and cardiovascular events in patients with type 1 MI, type 2 MI, acute nonischemic myocardial injury and chronic myocardial injury. In addition, this thesis aimed to investigate the impact of common cardiovascular medications within each type of myocardial injury. Methods: Patients with myocardial injury (i.e., high-sensitivity cardiac troponin T (hscTnT)>14 ng/L) identified from a cohort of patients from the emergency department with at least one visit for chest pain at the Karolinska University Hospital 2011 and 2014 were included in the studies. The cohort was obtained from the local administrative database that includes all patients seeking medical attention in the ED, while additional data were obtained from national registers. Study I was performed to investigate the long-term outcome in patients (n=3 853) with hs-cTnT levels>14 ng/L who were categorized as: type 1 MI, type 2 MI, acute nonischemic myocardial injury, and chronic myocardial injury. Study II was performed to investigate the causes of death in patients with myocardial injury compared with those without myocardial injury (hs-cTnT<14ng/L), who died during follow-up (n=2 285). Study III was performed to investigate how the number of commonly prescribed cardiovascular drugs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, statins, and platelet inhibitors) impacts mortality and cardiovascular events in patients with different types of myocardial injury. Study IV was performed to investigate whether prescribed high-, medium-, and low-intensity statin therapy impacts risks and outcomes in patients with different types of myocardial injury. Results: Patients with acute nonischemic myocardial injury and type 2 MI had a high risk of death, similar to patients with chronic myocardial injury, according to the findings of Study I. During a mean 4-year follow-up, nearly half of all patients in groups without type 1 MI died. Patients with nonischemic myocardial injury and patients with type 1 MI had similar high risk of cardiovascular death compared to patients with no myocardial injury. Patients with type 2 MI and chronic myocardial injury treated with 4 common cardiovascular drugs has a lower adjusted risk of death. Patients with nonischemic myocardial injury treated with two or three medications had a lower adjusted mortality risk compared to patients treated with zero or one medication. Patients with nonischemic myocardial injury and type 2 MI treated with high-intensity treatment had lower crude risks compared to patients treated with low-intensity treatment in corresponding groups, but estimates were not significant after adjusting for confounders. Conclusions: Patients with nonischemic myocardial injury and type 2 MI have a high risk of all-cause mortality and share similar risks for cardiovascular death as patients with type 1 MI. Patients with nonischemic myocardial injury and type 2 MI may benefit from common cardiovascular medications. Currently no clinical recommendations are available for how patients with nonischemic myocardial injury or type 2 MI should be managed, and this warrants further attention

Evaluation of cone beam computed tomography with respect to effective radiation dose and diagnostic properties

Cone beam computed tomography (CBCT) is an x-ray modality providing three-dimensional x-ray images. CBCT devices have high resolution compared to traditional medical CT, making them suitable for examination of fine details. However, CBCT devices are worse at showing contrast differences, making them less suitable for examinations of soft tissue such as the brain and many other internal organs. An x-ray modality suitable for imaging of small details and hard tissue fits dental and maxillofacial radiology well. After the introduction of dentomaxillofacial CBCT in 1998, CBCT examinations have spread to become a common and important diagnostic tool in odontology. Today, CBCT examinations complement or replace examinations previously performed by other methods. When choosing an x-ray imaging modality and examination parameters, concern must be taken for the diagnostic value and the radiation dose. The examination should be chosen to provide as low radiation dose as possible while not sacrificing the diagnostic value. In order to provide guidelines on the use of CBCT, scientific knowledge on CBCT and alternative examinations are needed. What is the radiation dose for different examinations and how does the examination affect diagnosis and treatment? This thesis aims to provide additional information in this field, to provide reference data when considering the choice of examination and the establishment of guidelines. In the first paper, examinations of the temporomandibular joint, using CBCT and traditional medical multi-detector CT (MDCT), were compared to determine if CBCT examinations would result in lower radiation dose. The examinations were optimized to find the lowest suitable dose levels, and at these optimized dose levels no significant difference was found between CBCT and MDCT. The second paper investigated the radiation dose from multiple different x-ray examinations of possible resorption impacted maxillary canines in children. CBCT examinations were compared to two-dimensional examinations using intraoral radiographs, and in some cases panoramic radiographs. CBCT examinations ranged from 15 to 140 times higher radiation dose, depending on x-ray device. The third paper investigated the possibility of reducing the image size, and therefore the x-ray dose, in panoramic radiographs. A full-size panoramic radiograph was required in 20% of adult patient cases. The introduction of two different image sizes for adult patients would reduce the collective radiation dose from panoramic examinations by about 40% in our university clinic. The fourth paper investigated radiation doses from different examinations and settings using the Newtom 5G CBCT device. This CBCT model use automatic exposure control and does not allow manual adjustment of exposure parameters. The resulting effective doses should be applicable to examinations of adult patients using this CBCT model

Why Bother About Clumsiness? The Implications of Having Developmental Coordination Disorder (DCD)

Developmental coordination disorder (DCD) is a common motor problem affecting—even in rather severe form—several percent of school age children. In the past, DCD has usually been called ‘clumsy child syndrome’ or ‘non-cerebralpalsy motor-perception dysfunction’. This disorder is more common in boys than in girls and is very often associated with psychopathology, particularly with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders/ autistic-type problems. Conversely, children with ADHD and autism spectrum problems, particularly those given a diagnosis of Asperger syndrome, have a very high rate of comorbid DCD. Psychiatrists appear to be unaware of this type of comorbidity in their young patients. Neurologists, on the other hand, usually pay little attention to the striking behavioral and emotional problems shown by so many of their ‘clumsy’ patients. A need exists for a much clearer focus on DCD—in child psychiatry and in child neurology—both in research and in clinical practice

Children screening positive for language delay at 2.5 years: language disorder and developmental profiles

Purpose: To characterize language disorder and developmental profiles in children who screened positive for language delay but negative for autism at 2.5 years of age. Patients and methods: The first 100 children who screened positive for language delay – but negative for autism – in 2016 were assessed in detail by speech language pathologists. Parents completed a newly developed questionnaire covering eight domains – Motor, Executive functions, Perception, Memory, Language, Learning, Social skills and Child’s behaviour – with impairment scored for each domain. Results: ICD-10 language disorder diagnoses were made in 87/100 children (29 girls, 58 boys). Of 52 children with mixed receptive–expressive language disorder, 32% had problems in other developmental areas according to the “global rating” in the impairment questions of the questionnaire. Of the 35 with expressive language disorder, 21% had problems in other areas according to the impairment questions. Thirteen children had isolated language delay with no other diagnoses according to the speech and language pathologists’ assessment; however, 23% of them had problems according to the parental rating on the impairment questions. Conclusion: Most children screening positive for language delay but negative for autism at age 2.5 years were diagnosed with ICD-10 language disorder diagnoses. Parents in about one in four cases reported impairing problems within other developmental areas. Possible explanations for the findings are discussed

Development problems were common five years after positive screening for language disorders and, or, autism at 2.5 years of age

Aim: This study identified whether children who had screened positive for either developmental language disorder (DLD) or autism spectrum disorder (ASD) at the age of 2.5 years had neurodevelopmental assessments five years later. Methods: Our study cohort were 288 children born from 1 July 2008 to 20 June 2009 who screened positive for DLD and, or, ASD at 2.5 years. Of these, 237 children were referred to, and assessed, at the Paediatric Speech and Language Pathology clinic (n = 176) or the Child Neuropsychiatry Clinic (n = 61) at the Queen Silvia Children's Hospital, Gothenburg, Sweden. Clinical registers covering all relevant outpatient clinics were reviewed five years later with regard to established diagnoses. Results: When the 237 were followed up five years later, 96 (40%) had established neurodevelopmental disorders or problems, often beyond DLD and ASD. Co‐existing problems were common in this cohort and multidisciplinary assessments were indicated. The other 60% did not appear in subsequent clinic records. It is likely that this 40% was a minimum rate and that more children will be referred for developmental problems later. Conclusion: Five years after they had been screened positive for DLD and, or autism at2.5 years, 40% of our cohort had remaining or other developmental problems

Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/ hyperactivity disorder

Objective: The primary objective of this study was to assess the impact of atomoxetine in combination with psychoeducation, compared with placebo and psychoeducation, on health-related quality of life (HRQL) in Swedish stimulant-naïve pediatric patients with attention deficit/ hyperactivity disorder (ADHD). HRQL results will be presented elsewhere. Here, psychoeducation as well as efficacy and safety of the treatment are described. Patients and methods: A total of 99 pediatric ADHD patients were randomized to a 10-week double-blind treatment with atomoxetine (49 patients) or placebo (50 patients). Parents of all patients received four sessions of psychoeducation. Atomoxetine was dosed up to approximately 1.2 mg/kg day (≤70 kg) or 80 mg/day (>70 kg). Improvement of ADHD symptoms was evaluated using the ADHD rating scale (ADHD-RS) and clinical global impression (CGI) rating scales. Safety was assessed based on adverse events (AEs). Results: The study population was predominantly male (80.8%) and diagnosed with the combined ADHD subtype (77.8%). The least square mean (lsmean) change from baseline to endpoint in total ADHD-RS score was −19.0 for atomoxetine patients and −6.3 for placebo patients, resulting in an effect size (ES) of 1.3 at endpoint. Treatment response (reduction in ADHD-RS score of ≥25 or ≥40%) was achieved in 71.4 or 63.3% of atomoxetine patients and 28.6 or 14.3% of placebo patients. The lsmean change from baseline to endpoint in CGI-Severity was −1.8 in the atomoxetine group compared with −0.3 in the placebo group. The difference between treatments in CGI-Improvement at endpoint was −1.4 in favor of atomoxetine. No serious AEs occurred. The safety profile of atomoxetine was in line with the current label. Conclusions: Atomoxetine combined with psychoeducation was superior to placebo and psychoeducation in ADHD core symptoms improvement. The large ES might be a result of including stimulant-naïve patients only, but also may indicate a positive interaction between atomoxetine treatment and psychoeducation, possibly by increased compliance

ADHD: Is There an App for That? A Suitability Assessment of Apps for the Parents of Children and Young People With ADHD

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a highly comorbid disorder that can impact significantly on the individual and their family. ADHD is managed via pharmacological and nonpharmacological interventions. Parents also gain support from parent support groups, which may include chat rooms, as well as face-to-face meetings. With the growth of technology use over recent years, parents have access to more resources that ever before. A number of mobile apps have been developed to help parents manage ADHD in their children and young people. Unfortunately many of these apps are not evidence-based, and little is known of their suitability for the parents or whether they are helpful in ADHD management. OBJECTIVE: The aim of this study was to explore the (1) parents' views of the suitability of the top ten listed apps for parents of children and young people with ADHD and (2) the views of clinicians that work with them on the suitability and value of the apps. METHODS: The top 10 listed apps specifically targeted toward the parents of children and young people with ADHD were identified via the Google Play (n=5) and iTunes store (n=5). Interviews were then undertaken with 7 parents of children or young people with ADHD and 6 clinicians who specialize in working with this population to explore their opinions of the 10 apps identified and what they believe the key components are for apps to be suitable and valuable for this population. RESULTS: Four themes emerged from clinician and parent interviews: (1) the importance of relating to the app, (2) apps that address ADHD-related difficulties, (3) how the apps can affect family relationships, and (4) apps as an educational tool. Two additional themes emerged from the clinician interviews alone: monitoring ADHD symptoms and that apps should be practical. Parents also identified an additional theme: the importance of the technology. Overall, the characteristics of the current top 10 listed apps did not appear to match well to the views of our sample. CONCLUSIONS: Findings suggest that these apps may not fully meet the complex needs of this parent population. Further research is required to explore the value of apps with this population and how they can be tailored to their very specific needs

Attention Deficit Hyperactivity Disorder: Is There an App for That? Suitability Assessment of Apps for Children and Young People With ADHD

Background: Attention-deficit/hyperactivity disorder (ADHD) is a complex highly comorbid disorder, which can have a huge impact on those with ADHD, their family, and the community around them. ADHD is currently managed using pharmacological and nonpharmacological interventions. However, with advances in technology and an increase in the use of mobile apps, managing ADHD can be augmented using apps specifically designed for this population. However, little is known regarding the suitability and usability of currently available apps. Objective: The aim of this study was to explore the suitability of the top 10 listed apps for children and young people with ADHD and clinicians who work with them. It is hypothesized that mobile apps designed for this population could be more suitably designed for this population. Methods: The top 10 listed apps that are specifically targeted toward children and young people with ADHD in the United Kingdom were identified via the Google Play (n=5) and iTunes store (n=5). Interviews were then undertaken with 5 clinicians who specialize in treating this population and 5 children and young people with ADHD themselves, to explore their opinions of the 10 apps identified and what they believe the key components are for apps to be suitable for this population. Results: Five themes emerged from clinician and young people interviews: the accessibility of the technology, the importance of relating to apps, addressing ADHD symptoms and related difficulties, age appropriateness, and app interaction. Three additional themes emerged from the clinician interviews alone: monitoring symptoms, side effects and app effect on relationships, and the impact of common comorbid conditions. The characteristics of the apps did not appear to match well with the views of our sample. Conclusions: These findings suggest that the apps may not be suitable in meeting the complex needs associated with this condition. Further research is required to explore the value of apps for children and young people with ADHD and their families and, in particular, any positive role for apps in the management of ADHD in this age group. A systematic review on how technology can be used to engage this population and how it can be used to help them would be a useful way forward. This could be the platform to begin exploring the use of apps further

Atomoxetine improves patient and family coping in attention deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled study in Swedish children and adolescents

This 10-week study assessed the efficacy of atomoxetine in combination with psychoeducation compared to placebo and psychoeducation in the improvement of Quality of Life in Swedish stimulant-naive children and adolescents with attention deficit/hyperactivity disorder. A total of 99 patients were treated with atomoxetine (49 patients) or placebo (50 patients) for 10 weeks and assessed regarding broader areas of functioning using the Quality of Life measures Child Health and Illness Profile-Child Edition (CHIP-CE), Family Strain Index [FSI; equivalent to the Family Burden of Illness Module used in the study], Appraisal of Stress in Child-Rearing (ASCR), Five to fifteen (FTF), “I think I am” (“Jag tycker jag är”), and Children’s Depression Rating Scale-Revised (CDRS-R) before and after the active treatment phase. Simultaneously, the patients’ parents participated in a 4-session psychoeducation program. A statistically significant difference in favor of atomoxetine was seen in the improvement from baseline to study endpoint for the CHIP-CE domains “Achievement” and “Risk avoidance”, for the FSI total score, for the ASCR section (I) domain “Child as a burden”, for all FTF domains except for “Language and Speech”, and for the CDRS-R total score. No difference between treatment groups was observed in the patient-assessed evaluation of self-esteem using the “I think I am” scale. Atomoxetine combined with psychoeducation had a positive effect on various everyday coping abilities of the patients as well as their families during 10 weeks of treatment, whereas the patients’ self-image and the parents’ image of the climate in the family were not significantly improved