Vårdprocedurer ur barnets, vårdnadshavares och vårdpersonals perspektiv - En mixad pilotstudie.    AbstraktBakgrund: Barns delaktighet i vården är viktig och reglerad av lagar. Hälso- och sjukvårdspersonal måste balansera barnets behov och vårdnadshavares ansvar. Metoder som smärtlindring och pediatrisk sedering används för att underlätta vårdprocedurer med fokus på varje barns individuella behov och säkerhet. Motiv: Sjukvårdsbesök kan vara skrämmande för barn. Vårdpersonalens ansvar är att stödja både barn och vårdnadshavare för att främja delaktighet. Det handlar om att lyssna på barnets tankar och ge anpassad information. Det finns därför behov av att undersöka hur vårdprocedurer upplevs ur alla inblandades perspektiv med särskilt fokus på delaktighet. Syfte: Pilotstudiens syfte är dels att testa ett frågeformulär, dels att belysa erfarenheter av delaktighet vid procedurer inom barnsjukvården, såväl med som utan sedering, ur barnets, vårdnadshavares och sjukvårdspersonalens perspektiv.  Metod: Pilotstudien använde mixad metod med konvergent parallell design som en del av projektet "Se mig, hör mig, möt mig", som fokuserar på erfarenheter ur olika inblandades perspektiv. Studien använde ett strategiskt urval för att samla in data från barn, vårdnadshavare och vårdpersonal involverade i olika medicinska procedurer. Både kvalitativ innehållsanalys och deskriptiv statistisk analys genomfördes för att analysera data. Resultat: Sammanfattningsvis visade pilotstudien att deltagarna var övervägande positiva till sin erfarenhet av en vårdprocedur genomförd med eller utan sedering. Men motsatsen framkom också genom att vissa av vårdnadshavarnas frågeformulär var av helt annan upplevelse. Resultatet visar att barn i större utsträckning upplever sig delaktiga i vården kontra vårdnadshavarna. De frågor som behandlade samma område ställdes emot varandra i ett sammanvägt resultat.   Konklusion: Studien indikerar positiva uppfattningar om barns deltagande inom sjukvården, med skillnader mellan vårdgivare, vårdnadshavare och barn. En klinisk implikation är genom att utvärdera deltagande före och efter standardens implementering, se om iSupport kan förbättra vården.

<p>Despite major advances in our understanding of the biology of childhood acute myeloid leukemia (AML) and the development of new cytotoxic drugs, the prognosis of long-term survival is still only 60-65 %.</p><p>In the present research, we studied the pharmacokinetics of drugs used in the induction therapy of childhood AML and performed in vitro drug sensitivity testing of leukemic cells from children with AML.</p><p>The aims of the studies were to correlate the results of the analysis to biological and clinical parameters and to identify subgroups of AML with specific drug sensitivity profiles in order to better understand why treatment fails in some patients and how therapy may be improved.</p><p>Blood samples were analysed to study the pharmacokinetics of doxorubicin (n=41), etoposide (n=45) and 6-thioguanine (n=50). Doxorubicin plasma concentration and total body clearance were correlated to the effect of induction therapy, and doxorubicin plasma concentration was an independent factor for complete remission, both in univariate and multivariate analysis including sex, age, and white blood cell count at diagnosis. For etoposide and 6-thioguanine no correlation was found between pharmacokinetics and clinical effect. Children with Down syndrome (DS) tended to reach higher blood concentrations of etoposide and thioguanine nucleotides, indicating that dose reduction may be reasonable to reach the same drug exposure as in children without DS.</p><p>Leukemic cells from 201 children with newly diagnosed AML, 15 of whom had DS, were successfully analysed for in vitro drug sensitivity by the fluorometric microculture cytotoxicity assay (FMCA). We found that samples from children with DS were highly sensitive to most drugs used in AML treatment. In non-DS children, the t(9;11) samples were significantly more sensitive to cytarabine (p=0.03) and doxorubicin (p=0.035) than other samples. The findings might explain the very favorable outcome reported in children with DS and t(9;11)-positive AML. A specific drug resistance profile was found for several other genetic subgroups as well. A detailed study of MLL-rearranged leukemia showed that cellular drug sensitivity is correlated both to partner genes and cell lineage, findings that support the strategy of contemporary protocols to include high-dose cytarabine in the treatment of patients with MLL-rearrangement, both in AML and acute lymphoblastic leukemia (ALL).</p><p>Our results indicate that drug resistance and pharmacokinetic studies may yield important information regarding drug response in different sub-groups of childhood AML, helping us to optimize future chemotherapy in childhood AML.</p>

<p><strong>SAMMANFATTNING</strong></p><p><strong>Syfte: </strong>Att beskriva förekomst av posttraumatisk stress och behov av känslomässigt stöd bland föräldrar till barn med hjärntumör vid två månader efter barnets diagnos (T2) respektive 12 månader efter avslutad cytostatika-/strålbehandling eller 18 månader efter operation av barn som inte fått cytostatika-/strålbehandling (T6). Syftet var också att jämföra behovet av känslomässigt stöd bland föräldrar med möjlig PTSD och hos de föräldrar som inte visar symtom på möjlig PTSD vid T2 respektive T6. <strong>Urval:</strong> 42 föräldrar till barn med hjärntumör deltog i studien: 20 mödrar och 22 fäder. <strong>Metod: </strong>Designen var deskriptiv longitudinell. Nivåer av PTSS och förekomst av möjlig PTSD mättes med PTSD Checklist Civilian, föräldrars behov av känslomässigt stöd mättes med ett studiespecifikt formulär. <strong>Resultat:</strong> Nivåer av PTSS hos föräldrar till barn med hjärntumör var lägre vid T6 än vid T2. Vid T2 hade 17 % möjlig PTSD jämfört med 5 % vid T6. Behovet av att samtala med psykolog var oförändrat lågt mellan T2 och T6, men behovet minskade över tid gällande att samtala med läkare, sjuksköterska, kurator, partner, vänner och övriga. <strong>Slutsats: </strong>Även om nivåer av PTSS och behovet av känslomässigt stöd på gruppnivå minskar över tid, bör vårdpersonal ändå uppmärksamma förälderns individuella behov av stöd. <strong></strong></p> / <p><strong>ABSTRACT</strong></p><p><strong>Aim:</strong> To describe occurrence of posttraumatic stress and the need of emotional support among parents of children with brain tumour two months after the child has been diagnosed (T2) respectively 12 months after completed chemo-/radiotherapy or 18 months after surgery of those children who did not receive chemo-/radiotherapy (T6). The aim was also to compare the need of emotional support between parents with occurrence of potential PTSD and parents who did not show any symptoms of potential PTSD at T2 and T6 respectively. <strong>Sample:</strong> 42 parents of children with brain tumour participated in the study: 20 mothers and 22 fathers. <strong>Method:</strong> The design was descriptive longitudinal. Levels of PTSS and occurrence of potential PTSD was measured by PTSD Checklist Civilian. Parents’ need of emotional support was measured with a study specific questionnaire. <strong>Results:</strong> Levels of PTSS was lower at T6 than T2. At T2 17 % had possible PTSD compared with 5 % at T6. The need to talk to a psychologist was unchanged low between T2 and T6, but the need declined over time concerning to talk with a doctor, nurse, welfare officer, partner, friends and others. <strong>Conclusion:</strong> Even if levels of PTSS and the need of emotional support in group level decline over time, nursing staff should still be ware of the parents’ individual need of support.</p>

<p><i>Chlamydia pneumoniae</i> is a human respiratory tract pathogen. Seroepidemiological studies indicate that <i>C. pneumoniae</i> infection is most common in school-aged children and infrequently detected in younger children.</p><p>The aims of this study were to further elucidate the prevalence of <i>C. pneumoniae</i> in paediatric populations and to describe the clinical implications of these infections.</p><p>The study population consisted of 367 children with respiratory tract diseases, 453 presumed healthy children at day-care, 69 children undergoing adenoidectomy and 1585 children from a population based cohort. Family members to infected day-care children were investigated. The laboratory methods used were polymerase chain reaction (PCR) on specimen from upper respiratory tract, serology by microimmunofluorescence (MIF), and immunohistochemistry (IHC) on adenoid tissue specimen. Personal data and medical history were obtained by the means of questionnaires and by the study of patient records.</p><p>In children younger than five years, the prevalence of <i>C. pneumoniae</i> was 17% as detected by PCR. This prevalence started to increase with increasing age from two years of age. The corresponding increase in serology as detected by MIF started at the age of four years. The prevalence at day-care centres varied from 4 to 39%. Both PCR and MIF underestimated the prevalence of <i>C. pneumoniae</i> detected by IHC. Families to infected children were investigated: mothers were more often infected than fathers were.</p><p>Most <i>C. pneumoniae</i> infections in small children were confined to the upper respiratory tract. These infections were usually mild or asymptomatic. Symptomatic disease may be of prolonged nature. No subsequent illness after <i>C. pneumoniae</i> infection was detected at follow-up after four years. In general, no association between <i>C. pneumoniae</i> and asthma was found, but <i>C. pneumoniae</i> may be of importance for asthma in some susceptible individuals. Previous <i>C. pneumoniae</i> infection reduced the risk for later atopy.</p><p>In conclusion, <i>C. pneumoniae</i> is a common finding in small children and most often causes relatively mild disease. If the acquisition of this infection early in life will have any implications for future health remains to be investigated.</p>

<p>Excessive weight gain has frequently been reported in adolescents with type 1 diabetes, especially in girls. In general, puberty is associated with reduced insulin sensitivity that is further diminished by overweight. The causes and consequences of excessive weight gain in adolescents with type 1 diabetes are not fully understood. The studies described in this thesis addressed body composition in adolescents with type 1 diabetes and the relationships between physical activity, energy intake and changes in body composition. Furthermore, the effect of metformin as additional therapy on glycaemic control and insulin sensitivity was examined in a randomised placebo-controlled study. Body mass index (BMI) and percentage body fat (%BF) were significantly higher in girls with type 1 diabetes compared to healthy control girls. Mean HbA1c during puberty, but not mean insulin dose, was positively related to BMI at the age of 18 in girls with diabetes. A centralised fat distribution was associated with poor glycaemic control, increased daily dosage of insulin and elevated cholesterol and triglyceride levels. Neither total physical activity nor total energy intake differed between adolescent girls with type 1 diabetes and healthy age-matched control girls. A high dietary fat intake was positively related to gain in %BF in girls with type 1 diabetes. Additional therapy with metformin for three months improved glycaemic control and peripheral insulin sensitivity in adolescents with poorly controlled type 1 diabetes. The improvement in glycaemic control was related to insulin sensitivity at baseline, implying that the most insulin resistant subjects benefited most from the metformin therapy. It is concluded that the excessive weight gain observed in girls with type 1 diabetes is mainly attributable to an increased fat mass and that dietary fat intake is of importance for this gain in body fat. Additional treatment with metformin improves glycaemic control in adolescents with poorly controlled type 1 diabetes.</p>

<p>The process of β-cell destruction that leads to type 1 diabetes (T1D) is incompletely understood and it is believed to be a result of both genetic and environmental factors. Enterovirus (EV) infections of the β-cells have been proposed to be involved, however, the effects of EV infections on human β-cells have been little investigated. This thesis summarises studies of three different Coxsackie B4 virus strains that have previously been shown to infect human islets. The effects of infections with these EV were studied <i>in vitro</i> in human islets and in a rat insulin-producing cell line. In addition, a pilot study was performed on isolated human islets to investigate the ability to treat such infections with an antiviral compound.</p><p>It was found that one of the virus strains replicated in human β-cells without affecting their main function for at least seven days, which <i>in vivo</i> may increase a virus’s ability to persist in islets.</p><p>Nitric oxide was induced by synthetic dsRNA, poly(IC), but not by viral dsRNA in rat insulinoma cells in the presence of IFN-γ, suggesting that this mediator is not induced by EV infection in β-cells and that poly(IC) does not mimic an EV infection in this respect.</p><p>All three virus strains were able to induce production of the T-cell chemoattractant interferon-γ-inducible protein 10 (IP-10) during infection of human islets, suggesting that an EV infection of the islets might trigger insulitis <i>in vivo</i>.</p><p>Antiviral treatment was feasible in human islets, but one strain was resistant to the antiviral compound used in this study.</p><p>To conclude, a potential mechanism is suggested for the involvement of EV infections in T1D. If EV infections induce IP-10 production in human islet cells <i>in vivo</i>, they might recruit immune cells to the islets. Together with viral persistence and/or virus-induced β-cell damage, this might trigger further immune-mediated β-cell destruction <i>in vivo</i>.</p>

Chlamydia pneumoniae is a human respiratory tract pathogen. Seroepidemiological studies indicate that C. pneumoniae infection is most common in school-aged children and infrequently detected in younger children. The aims of this study were to further elucidate the prevalence of C. pneumoniae in paediatric populations and to describe the clinical implications of these infections. The study population consisted of 367 children with respiratory tract diseases, 453 presumed healthy children at day-care, 69 children undergoing adenoidectomy and 1585 children from a population based cohort. Family members to infected day-care children were investigated. The laboratory methods used were polymerase chain reaction (PCR) on specimen from upper respiratory tract, serology by microimmunofluorescence (MIF), and immunohistochemistry (IHC) on adenoid tissue specimen. Personal data and medical history were obtained by the means of questionnaires and by the study of patient records. In children younger than five years, the prevalence of C. pneumoniae was 17% as detected by PCR. This prevalence started to increase with increasing age from two years of age. The corresponding increase in serology as detected by MIF started at the age of four years. The prevalence at day-care centres varied from 4 to 39%. Both PCR and MIF underestimated the prevalence of C. pneumoniae detected by IHC. Families to infected children were investigated: mothers were more often infected than fathers were. Most C. pneumoniae infections in small children were confined to the upper respiratory tract. These infections were usually mild or asymptomatic. Symptomatic disease may be of prolonged nature. No subsequent illness after C. pneumoniae infection was detected at follow-up after four years. In general, no association between C. pneumoniae and asthma was found, but C. pneumoniae may be of importance for asthma in some susceptible individuals. Previous C. pneumoniae infection reduced the risk for later atopy. In conclusion, C. pneumoniae is a common finding in small children and most often causes relatively mild disease. If the acquisition of this infection early in life will have any implications for future health remains to be investigated.

Excessive weight gain has frequently been reported in adolescents with type 1 diabetes, especially in girls. In general, puberty is associated with reduced insulin sensitivity that is further diminished by overweight. The causes and consequences of excessive weight gain in adolescents with type 1 diabetes are not fully understood. The studies described in this thesis addressed body composition in adolescents with type 1 diabetes and the relationships between physical activity, energy intake and changes in body composition. Furthermore, the effect of metformin as additional therapy on glycaemic control and insulin sensitivity was examined in a randomised placebo-controlled study. Body mass index (BMI) and percentage body fat (%BF) were significantly higher in girls with type 1 diabetes compared to healthy control girls. Mean HbA1c during puberty, but not mean insulin dose, was positively related to BMI at the age of 18 in girls with diabetes. A centralised fat distribution was associated with poor glycaemic control, increased daily dosage of insulin and elevated cholesterol and triglyceride levels. Neither total physical activity nor total energy intake differed between adolescent girls with type 1 diabetes and healthy age-matched control girls. A high dietary fat intake was positively related to gain in %BF in girls with type 1 diabetes. Additional therapy with metformin for three months improved glycaemic control and peripheral insulin sensitivity in adolescents with poorly controlled type 1 diabetes. The improvement in glycaemic control was related to insulin sensitivity at baseline, implying that the most insulin resistant subjects benefited most from the metformin therapy. It is concluded that the excessive weight gain observed in girls with type 1 diabetes is mainly attributable to an increased fat mass and that dietary fat intake is of importance for this gain in body fat. Additional treatment with metformin improves glycaemic control in adolescents with poorly controlled type 1 diabetes.

The process of β-cell destruction that leads to type 1 diabetes (T1D) is incompletely understood and it is believed to be a result of both genetic and environmental factors. Enterovirus (EV) infections of the β-cells have been proposed to be involved, however, the effects of EV infections on human β-cells have been little investigated. This thesis summarises studies of three different Coxsackie B4 virus strains that have previously been shown to infect human islets. The effects of infections with these EV were studied in vitro in human islets and in a rat insulin-producing cell line. In addition, a pilot study was performed on isolated human islets to investigate the ability to treat such infections with an antiviral compound. It was found that one of the virus strains replicated in human β-cells without affecting their main function for at least seven days, which in vivo may increase a virus’s ability to persist in islets. Nitric oxide was induced by synthetic dsRNA, poly(IC), but not by viral dsRNA in rat insulinoma cells in the presence of IFN-γ, suggesting that this mediator is not induced by EV infection in β-cells and that poly(IC) does not mimic an EV infection in this respect. All three virus strains were able to induce production of the T-cell chemoattractant interferon-γ-inducible protein 10 (IP-10) during infection of human islets, suggesting that an EV infection of the islets might trigger insulitis in vivo. Antiviral treatment was feasible in human islets, but one strain was resistant to the antiviral compound used in this study. To conclude, a potential mechanism is suggested for the involvement of EV infections in T1D. If EV infections induce IP-10 production in human islet cells in vivo, they might recruit immune cells to the islets. Together with viral persistence and/or virus-induced β-cell damage, this might trigger further immune-mediated β-cell destruction in vivo.

Type 1 diabetes (T1D) is a chronic disease caused by destruction of the insulin producing beta-cells in the pancreas. The incidence of T1D has increased rapidly, especially in the Western world and among young children. The pathogenesis of T1D is not fully understood, but the beta-cells are believed to be destroyed by an autoimmune process initiated years before the onset of T1D. During this pre-clinical period, autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the tyrosine phosphatase-like protein IA-2 (IA-2A) can be detected and are used to identify individuals at risk of T1D. The major genetic determinant for T1D is the HLA class II genes, but also polymorphism in the insulin gene and CTLA-4 gene are associated with T1D. The risk genes cannot explain the rapid increase in incidence of T1D, therefore a role for different environmental factors has been suggested. The aim was to study the prevalence of beta-cell autoantibodies in children from the general population in relation to known genetic and environmental risk factors, and in young patients with T1D in high and low incidence areas. Short duration of breast-feeding was associated with an increased risk of developing beta-cell autoantibodies in children from the general population at 5-6 years of age. We found an association between positivity for GADA and/or IAA at the age of 5-6 years and a short duration of total breastfeeding, and also between positivity for GADA, IA-2A and/or IAA and a short duration of exclusive breast-feeding. Our findings suggest that breast-feeding has a long term protective effect on the risk of beta-cell autoimmunity in children from the general population. The T1D related risk genes were not associated with beta-cell autoantibodies other than GADA in children from the general population at 5-6 years of age. Children with the DR4-DQ8 haplotype were more often positive for GADA than children without this haplotype. We found no association of GADA with DR3-DQ2 haplotype or between these two haplotypes and any of the other autoantibodies. Our results suggest that beta-cell autoimmunity in children from the general population is not strongly associated with any risk genes of T1D other than DR4-DQ8. In the non-diabetic children with allergic heredity GADA was detectable in almost all children, IA-2A in about half and IAA in 10% of the children. The levels low of these autoantibodies fluctuated with age and different patterns of fluctuations were seen for GADA and IA-2A, which may reflect differences in the immune response to the autoantigens. In patients with newly diagnosed T1D, we found some differences between patients from a high incidence country (Sweden) and a country with a lower incidence (Lithuania). Among the Swedish patients, the prevalence of IAA and GADA or multiple autoantibodies was higher than in Lithuanian patients. The risk genes DR4-DQ8 and the heterozygous high risk combination DR4-DQ8/DR3-DQ2 was more common among the Swedish patients than Lithuanian patients. Patients with low levels of IAA had higher levels of HbA1c and ketones, indicating that patients without IAA or with low levels of IAA have a more severe onset of T1D. Our findings indicate that beta-cell autoimmunity is more pronounced in a high incidence area compared to an area with a lower incidence. In conclusion, short duration of breast-feeding is a risk factor for beta-cell autoantibodies in children from the general population, and the beta-cell autoantibodies in these children are not associated with specific risk genes. Children with newly diagnosed T1D in a high incidence area carry risk genes and have autoantibodies more often than newly diagnosed children from an area with a lower incidence, perhaps indicating different disease phenotypes.