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Background: Coronary Artery Disease (CAD) represents the leading cause of mortality and morbidity worldwide despite declines in the prevalence of environmental risk factors. This trend has drawn attention to the risk conferred by genetic variation. Twin and linkage studies demonstrate a profound hereditary risk for CAD, especially in young individuals. Rare genetic variants conferring high risk for extreme disease phenotypes can provide invaluable insight into novel mechanisms underlying CAD development. Methods: Whole exome sequencing was performed to characterize rare protein-altering variants in 52 early-onset CAD (EOCAD) patients encompassing the DECODE study. The enrichment of Mendelian dyslipidemias in EOCAD was assessed through interrogation of pathogenic mutations among known lipid genes. The identification of novel genetic CAD associations was conducted through case-only and case-control approaches across all protein-coding genes using rare variant burden and variance component tests. Lastly, beta coefficients for significant risk genes from the European population in the Early-onset Myocardial Infarction (EOMI) cohort (N=552) were used to construct calibrated, single-sample rare variant gene scores (RVGS) in DECODE Europeans (N=39) and a local European CAD-free cohort (N=77). Results: A 20-fold enrichment of Familial hypercholesterolemia mutation carriers was detected in EOCAD cases compared to CAD-free controls (P=0.005). Association analysis using EOMI Europeans revealed exome-wide and nominal significance for two known CAD/MI genes: CELSR2 (P=1.1x10-17) and APOA5 (P=0.001). DECODE association revealed exome-wide and nominal significance for genes involved in endothelial integrity and immune cell activity. RVGS based upon beta coefficients of significant CAD/MI risk genes were significantly increased in DECODE (z-score=1.84; p=0.03) and insignificantly decreased among CAD-free individuals (z-score=-1.61; p=0.053). Conclusion: Rare variants play a pivotal role in the development early CAD through Mendelian and polygenic mechanisms. Construction of RVGS that are calibrated against population and technical biases can facilitate discovery of single-sample and cohort-based associations beyond what is detectable using standard methods. / Thesis / Master of Science (MSc)

: la schizophrénie à début précoce (SDP) est un syndrome rare invalidant peu étudié. Dans ce travail, nos objectifs sont: de caractériser de profils cliniques des SDP via une approche développementale et dimensionnelle; de poser un diagnostic étiologique des formes organiques; d'analyser la reconnaissance émotionnelle dans la SDP. Méthodologie: Dans une cohorte d'enfants atteints de SDP (N=90) j'ai développé et validé une méthode de psychométrie quantitative en utilisant une échelle spécifique Lifetime Dimensions of Psychosis Scale - Children and Adolescents; des données de psychologie expérimentale; de génétique. Résultats: en appliquant une évaluation développementale et dimensionnelle, j'ai identifié 6 profils cliniques dans la cohorte SDP. L'analyse par clusters retrouve 3 groupes, dont le cluster plus significatif est caractérisé par une sévérité importante des symptômes positifs et de ceux positifs bizarres. Ce cluster montre une association modérée entre la sévérité des symptômes positifs bizarres et les anomalies du développement. Dans une perspective étiologique des SDP, j'ai proposé une série d'explorations médicales de premier rang afin d'éliminer une SDP organique. J'ai décrit le cas clinique d'un patient porteur d'une délétion de 1,9 Mb dans la région 8p23.2 qui pourrait entrainer une perte de fonction du gène CSMD1, dont la protéine est impliquée dans la régulation immunitaire du développement cérébral. J'ai intégré à ce travail une étude de psychologie expérimentale appliquée à la SDP. Cette étude est la première à avoir exploré le rôle de l'intégration multi-sensorielle dans la reconnaissance émotionnelle dans une perspective développementale chez des patients atteints de SDP. Conclusion: la SDP est un trouble cliniquement hétérogène dont l’étiologie est inconnue et dont la compréhension des différents mécanismes physiopathologiques pourrait contribuer à des nouvelles stratégies thérapeutiques. / Early Onset Schizophrenia (EOS) is a severe but rare disorder in children. Focusing on developmental pathways to EOS, this work aims: to describe different developmental profiles that contribute to EOS phenotypes using a dimensional perspective; to study medical conditions associated with EOS using multidisciplinary search; to assess emotional recognition as key factor of social interaction. Methods: In a cohort of 90 children with EOS, I applied quantitative psychometric methods with development and validation of a specific scale; experimental psychology; molecular cytogenetics. Results: using a dimensional and developmental evaluation (Lifetime Dimensions of Psychosis Scale – Children Adolescents), I identified symptom profiles. In EOS cohort, 6 dimensional factors were identified. 64% of sample had premorbid developmental or learning problems. Cluster analysis delineated 3 groups: the largest cluster including 58% of the patients was characterized by high Positive and Bizarre Positive scores and fewer (28%) developmental abnormalities. I also reviewed numerous likely organic causalities in EOS. I proposed a systematic algorithm to better assess these conditions by focusing on treatable ones. I detailed a case report on an adolescent with EOS carrier of a rare CNV implicated in the immune modulation of cerebral pruning. Assessing emotional recognition, empathy development and non verbal communication, I found that EOS patients performed worse than healthy controls in emotional tasks, with a significant association between emotional identification scores and nonverbal communication impairments. This means that cumulative dysfunctions in both nonverbal communication and emotion processing contribute to the social vulnerability found in youths with EOS. Conclusion: EOS is a complex condition with unknown etiology. How the understanding of specific etiologies may lead to new therapeutic approaches is the next challenge.

Early onset depression is associated with high recurrence rates later in life. Recurrent depressive episodes during childhood may be particularly problematic, if additional episodes have a scarring effect that hinders healthy development. Distinguishing between first onsets and recurrences has been useful in understanding adult depression. This distinction has seldom been examined in pediatric depression, in part because it is difficult to enroll adequate samples of children with recurrent depression. We conducted archival analyses of carefully-diagnosed pediatric probands with depression first onset between ages of 4 and 12. Probands who reported one depressive episode (N = 435) were compared with probands who reported two depression episodes (N = 115) on clinical (treatment, comorbidities), psychosocial (negative life events (NLEs), parental psychopathology) and emotion regulation measures. Based on previous findings in older adolescents and adults, we hypothesized that probands with two MDEs will have higher comorbidity, parental psychopathology, more NLEs, and higher maladaptive emotion regulation scale scores than probands with one MDE. Surprisingly, probands with one and two MDEs were indistinguishable on psychological and pharmacological treatment variables. As expected, probands with two MDEs had lower age of first onset, higher maladaptive emotion regulation scores, higher rates of comorbid anxiety and reported more NLEs than probands with one MDE. Probands with two MDEs also spent a longer total time in episode; group differences remained after controlling for time spent depressed. Distinguishing between first onsets and recurrences is meaningful in pediatric depression.

Tyrimo tikslas – nustatyti nėščių moterų B grupės β hemolizinio streptokoko (BGS) ir Escherichia coli (E.coli) nešiojimo bei naujagimių kolonizacijos dažnumą ir įvertinti šių mikroorganizmų įtaką naujagimių ankstyvai infekcijai atsirasti. Metodika. Perspektyvinis momentinis stebėjimo tyrimas vykdytas Kauno medicinos universiteto Akušerijos ir ginekologijos bei Neonatologijos klinikose. Moterims du atskiri pasėliai iš makšties apatinio trečdalio ir išangės buvo paimti 35-37 nėštumo savaitę arba gimdymo metu, o naujagimiams - iš ausies išorinės landos bei nosiaryklės per 5 – 15 min. po gimimo. Išskirtų BGS serotipavimas atliktas naudojant 9 specifinius antiserumus, o jautrumas antibiotikams nustatytas diskų difuzijos metodu pagal klinikinių laboratorijų standartus nustatančio komiteto (NCCLS) rekomendacijas. Rezultatai. Šimtas keturiasdešimt aštuonioms moterims iš 970 (15,3 proc.) buvo nustatytas BGS nešiojimas, o 193 moterims (19,9 proc.) - E.coli nešiojimas. Naujagimių BGS ir E.coli kolonizacijos dažnumas buvo 6,4 proc. ir 14,4 proc., o vertikalaus pernešimo – atitinkamai 28,4 ir 24,4 procentai. Moterims ir naujagimiams dažniausiai identifikuotas III ir Ia serotipo BGS. Bendras naujagimių įgimtos infekcijos dažnumas buvo 37,5 atvejai iš 1000 naujagimių, o BGS sukeltos infekcijos dažnumas - 3,6 atvejai iš 1000 naujagimių. Nebuvo nė vieno E.coli sukeltos ankstyvos naujagimių infekcijos atvejo. Klinikinis sepsis diagnozuotas 5 kartus dažniau nei mikrobiologiniais tyrimais... [toliau žr. visą tekstą] / Objective - to examine the prevalence of maternal and neonatal colonization of group B streptococcus (GBS) and Escherichia coli (E.coli) in our area, and to evaluate the colonization impact on early onset neonatal infections as a whole. Methods. A prospective cross-sectional study carried out at the Department of Obstetrics and Gynaecology and the Department of Neonatology of Kaunas University Hospital. Samples were collected from the lower vagina and the anorectum of pregnant women at 35-37 weeks of gestation or at delivery and the ear canal as well as throat of the neonates within 5 – 15 min of their lives. The distribution of serotypes of the GBS identified was determined using specific antisera and antimicrobial susceptibility was investigated by disc-diffusion method as described by National Committee for Clinical Laboratory Standards (NCCLS). Results. GBS carriage was detected in 148 (15.3%) of 970 women screened whereas E.coli colonisation was found in 193 (19.9%) of the women studied. The overall GBS and E.coli neonatal colonization rates were 6.4% and 14.4%; vertical transmission rates - 28.4% and 24.4%, respectively. The most common GBS serotypes were III and Ia. The overall incidence of early onset neonatal infection was estimated to be 37.5 per 1000 live birth and the incidence of early onset GBS disease in newborns – 3.6 per 1000 live birth. There was no case of early neonatal E. coli infection. The incidence of clinical sepsis in neonates was 5 fold higher that... [to full text]

Background: Dementia is a progressive and chronic syndrome that leads to deterioration incognitive functions. Early-onset dementia are symptoms of dementia under 65 years, such as behavioural changes, neurological disorder, and depression. It causes decreased capabilities, dependence, reduced initiative, and motivation. The individuals need help to function. Nursesand family caregivers help to care for them. Aim: The aim of this study was to describe nurses’ and family caregivers’ experiences incaring for persons with early-onset dementia. Method: A general literature review based on ten original articles with a qualitative approachand thematic analysis. Results: The material thematically analysed with three themes identified: a lack of knowledge, information, and support; psychological experience; negative and positive social experience. some of nurses’ experiences impacted them professionally; family caregivers were affected by physical, psychological, social, and economic hardship. Conclusion: The nurses experienced lack of support by the state to give evidence-based care. The family caregiver lacked financial and social support to care for EOD patients. i.e., both nurses and family caregivers have common experience in different ways. They helped to improve the EOD patient’s quality of life. The knowledge from the experiences will create a better understanding of the challenges and offer solutions. / Bakgrund: Demens är ett progressivt och kroniskt syndrom som leder till försämring av kognitiva funktioner. Tidig demens orsakar symtom före 65 års ålder. Sjukdomen kännetecknas av beteendeförändringar, neurologiska störningar och depression och leder ofta till en nedsatt funktionsförmåga, förlust av självständighet samt en minskad initiativförmåga och motivation. Sjuksköterskor och anhörigvårdgivare kan anses ha en nyckelroll i vård av denna patientgrupp med omfattande hjälpbehov. Syftet: Syftet med denna studie var att beskriva sjuksköterskors och anhörigvårdgivares upplevelser av omvårdnad av personer med tidig demenssjukdom. Metod: En allmän litteraturöversikt baserad på tio originalartiklar med kvalitativ ansats samt tematisk analys. Resultat: Materialet analyserades tematiskt och tre teman identifierades: Bristande kunskap, information och stöd; psykologisk upplevelse samt social upplevelse. En del av sjuksköterskors upplevelser hade en yrkesmässig inverkan på dem, anhörigvårdgivare däremot påverkades på det fysiska, psykologiska, sociala och ekonomiska planer. Slutsats: Sjuksköterskor saknade stöd från staten för att kunna ge evidensbaserad omvårdnad för denna patientgrupp. Anhörigvårdgivare saknade ekonomiskt och socialt stöd i sambandmed omvårdnad. Fynden kan bidra till en ökad livskvalité hos patienter med tidig demens, för att öka förståelsen för utmaningar hos denna patientgrupp samt för att hitta fungerande lösningar.

No description available.

Introduktion: Tidigt debuterande demenssjukdom (TDD) innebär att symtomen på demens debuterat innan 65 års ålder och är ovanligare än den geriatriska demensen. Dessa patienter och deras anhöriga möter andra utmaningar i vardagen än äldre patienter och deras anhöriga, med tanke på deras sociala roller i mitten av livet. Som sjuksköterska är det viktigt att förstå de anhörigas upplevelser för att kunna ge ett tillräckligt stöd till dem, då tidigare studier vittnar om att stödet är bristfälligt. Syfte: Att beskriva vuxna anhörigas upplevelse av att ha en närstående som fått en demensdiagnos med tidig debut.  Metod: Litteraturöversikt med deskriptiv design baserad på 13 originalstudier med kvalitativ ansats publicerade i PubMed. Resultat: De kategorier som framkom genom resultatanalysen var oro och kunskapsbrist relaterat till diagnosen, upplevelser av det nya vardagslivet, förändrade roller, den anhörigas fritid och jobb, ensamhet och stigma samt sorgeprocesser. De anhöriga upplevde främst negativa aspekter av att ha en närstående med TDD, däribland en ansträngd tid innan diagnos på grund av oförklarliga personlighetsförändringar, frustration, skuldkänslor, vårdarrollen, inskränkt fritid, social isolering, nedstämdhet men även vissa positiva erfarenheter framkom. Slutsats: Anhöriga till personer med TDD upplevde negativa känslor, förändringar samt hinder i livet kopplat till den tidiga demensdiagnosen. Det är av stor vikt för sjuksköterskan att vara medveten om dessa upplevelser för att kunna ge de anhöriga rätt stöd. / Introduction: Early onset dementia (TDD) implies a debut of symptoms before the age of 65 and is less common than the geriatric type. These patients and their families face different challenges in everyday life then the older patients and their families, hence their midlife social roles. As a nurse it is of importance to understand the experience of families to be able to offer enough support, since recent studies indicate there is a lack of support.      Purpose: To describe adult family members’ experiences of having a relative with early onset dementia. Method: Literature review with a descriptive design based on 13 primary research studies with a qualitative approach published in PubMed. Result: The categories that emerged through the analysis of the result was anxiety and a lack of knowledge related to the diagnosis, experiences of the new everyday life, changed roles, the family members recreational activities and occupation, loneliness and stigma as well as grieving processes. The family members mostly experienced negative aspects of having a relative with early onset dementia including a hard time before the diagnoses because of the unaccounted changes in behavior, frustration, guilt, the caring role, restricted recreational activities, social isolation, dejection but some positive experiences did appear Conclusion: Family members to relatives with early onset dementia experience negative feelings, changes and obstacles in life related to the early diagnosis of dementia. It is of great importance for the nurse to be aware of these experiences, to be able to provide the families with correct support.

Background: In preterm infants with premature rupture of membranes, antibiotic treatment is frequently started but rates of early onset sepsis are lower. In line with national guidelines, a stratified approach in the decision to start antibiotic treatment using maternal history, clinical impression and biomarkers has been implemented in our level III neonatal center and its results are evaluated. - Methods: Retrospective cohort study of all preterm newborns with rupture of membranes at least 1 h prior to delivery admitted to our tertiary neonatal intensive care unit. Data on antibiotic exposure, mortality and major neonatal complications were extracted from the electronic patient charts to evaluate the effects and safety of our stratified approach. - Results: Four hundred fifty-six infants met the inclusion criteria. 120 (26%) received primary antibiotics whereas 336 (74%) did not. Of those receiving primary antibiotics, 13 (11%) had a blood culture positive sepsis, 46 (38%) met the criteria of clinical sepsis and in 61 (51%) sepsis was ruled out and antibiotics were stopped after 48-96 h. All infants with blood culture positive sepsis were identified and treated within the first 24 h of life using this approach. None of the 336 infants who were not started on antibiotics primarily needed antibiotic therapy within the first 5 days of life. There were no deaths or major neonatal complications in the group that did not receive empiric antibiotics. - Conclusions: Our stratified approach for preterm infants with premature rupture of membranes allows a safe reduction of antibiotic exposure even in this high risk population. As a result, only 25% of high risk preterm newborns are treated with antibiotics of which more than half receive less than 5 days of treatment. To treat one infant with blood culture positive sepsis, only 9 infants receive empiric antibiotics.

Yes / Objectives: Young onset dementia is associated with distinctive support needs but existing research on service provision has been largely small scale and qualitative. Our objective was to explore service use, cost and satisfaction across the UK. Methods: Information about socio‐demographic characteristics, service use and satisfaction were gathered from people with young onset dementia (YOD) and/or a family member/supporter via a national survey. Results: Two hundred and thirty‐three responses were analysed. Diagnosis was most commonly received through a Memory Clinic or Neurology. The type of service delivering diagnosis impacted on post‐diagnostic care. Those diagnosed in specialist YOD services were more likely to receive support within the first 6 weeks and receive ongoing care in the service where they were diagnosed. Ongoing care management arrangements varied but generally care was lacking. Around 42% reported no follow‐up during 6‐weeks after diagnosis; over a third reported seeing no health professional within the previous 3 months; just over a third had a key worker and just under a third had a care plan. Satisfaction and quality of care were highest in specialist services. Almost 60% of family members spent over 5 h per day caring; median costs of health and social care, 3 months, 2018, were £394 (interquartile range £389 to 640). Conclusions: Variation across diagnostic and post‐diagnostic care pathways for YOD leads to disparate experiences, with specialist young onset services being associated with better continuity, quality and satisfaction. More specialist services are needed so all with YOD can access age‐appropriate care. / Alzheimer's Society. Grant Number: 278 AS-PG-15b-034