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- Johansson Kostenniemi, Urban, 1987-
(författare)
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Bacterial meningitis in children : clinical aspects and preventive effects of vaccinations
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bacterial meningitis, one of the most severe infections a child can contract, can be caused by several different strains of bacteria. Most commonly, Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and Neisseria meningitidis. These colonize the upper respiratory tract, then either cause localized infections acting as primary foci or directly spread to the brain. As preventive measure, general infant Hib and pneumococcal vaccinations were introduced in Sweden in 1993 and in 2009, respectively. Although evaluated extensively elsewhere, their long-term effects in Arctic regions are less studied. For the individual child with bacterial meningitis, treatment involves many challenges starting with correctly identifying the condition, guiding treatment, and finally identifying both short-term and long-term disabilities.In this thesis, the overall aim was to study clinical aspects of bacterial meningitis and preventive effects of vaccinations in an Arctic region. We used two datasets in the Västerbotten Region to investigate incidence rates during the time-periods adjacent to vaccine introductions. This allowed us to study the preventive effects of general infant vaccinations on bacterial meningitis in one of the Swedish Arctic regions. More precisely, we investigated changes in incidence of bacterial meningitis and sepsis during the period of 1986-2015 and of respiratory tract infections during the period of 2005-2014, in the Västerbotten Region, Sweden. We also reviewed medical records of children being treated for bacterial meningitis in the Västerbotten Region to study clinical presentation, short-term outcome, and to develop a new predictive score for identifying adverse outcome and need of invasive procedures. Additionally, by reviewing medical records and child health records from discharge and onwards we assessed long-term disabilities and evaluated clinical guidelines’ follow-up recommendations.Following introduction of general infant Hib vaccination, incidence of all-cause bacterial meningitis and Haemophilus meningitis in children aged one month to four years declined by 82.3% and 95.3%, respectively. Likewise, all-cause bacterial meningitis and pneumococcal meningitis declined by 48.0% and 67.5%, respectively, following pneumococcal vaccination. In addition, incidence of sepsis caused by H. influenzae and by S. pneumonia also decreased in the same age group. Finally, respiratory tract infections in children under five years of age decreased following pneumococcal vaccination; by 41.5% for all-cause acute otitis media, by 80.7% for sinusitis and by 28.6% for pneumonia.At admission to the hospital, difference in clinical presentation mostly depended on age. Younger children were more ill at admission but also presented with more diffuse symptoms. When evaluating clinical decision rules for detecting bacterial meningitis, none reached 100% sensitivity. The predictive score developed by us could identify all children in need of invasive procedures to manage the intracerebral pressure and were graded as excellent in the ROC analysis at this task. However, neither this score nor any other could adequately predict complications or death. Finally, permanent disabilities affected more than half of surviving children with psychiatric disease being diagnosed in 30%, and another 5% had ongoing investigations for symptoms of psychiatric disease. Notably, psychiatric disabilities were detected late, in average 14 years after having had bacterial meningitis.From these findings, we concluded that vaccinations are excellent at protecting children against bacterial meningitis, also in the Arctic region, with the added bonus of providing protection against sepsis and less severe infections such as pneumonia and acute otitis media. Further, treating children with bacterial meningitis involves several challenges starting with correctly identifying this sever disease. For this task, no clinical decision rule is perfect. When making difficult treatment decisions such as deciding on invasive procedures to manage the intracerebral pressure, the predictive score developed and tested by us, the MeningiSSS, can be very helpful. Finally, permanent disabilities may be more common than previously thought. With more than one third of survivors being affected by psychiatric disabilities, specific long-term follow-up strategies are needed to reduce suffering caused by undetected psychiatric disabilities.
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| 2. |
- Johansson Kostenniemi, Urban, 1987-, et al.
(författare)
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MeningiSSS : A New Predictive Score to Support Decision on Invasive Procedures to Monitor or Manage the Intracerebral Pressure in Children with Bacterial Meningitis
- 2020
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Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 32:2, s. 586-595
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Tidskriftsartikel (refereegranskat)abstract
- Background: Knowing the individual child’s risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors.Methods: We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure.Results: For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores’ results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson–Todd Scale (AUC = 0.79) was all associated with death.Conclusions: The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management.
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| 4. |
- Remes, K, et al.
(författare)
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Telomere length and telomerase activity in malignant lymphomas at diagnosis and relapse
- 2000
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 82:3, s. 601-607
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Tidskriftsartikel (refereegranskat)abstract
- Telomere length maintenance, in the vast majority of cases executed by telomerase, is a prerequisite for long-term proliferation. Most malignant tumours, including lymphomas, are telomerase-positive and this activity is a potential target for future therapeutic interventions since inhibition of telomerase has been shown to result in telomere shortening and cell death in vitro. One prerequisite for the suitability of anti-telomerase drugs in treating cancer is that tumours exhibit shortened telomeres compared to telomerase-positive stem cells. A scenario is envisioned where the tumour burden is reduced using conventional therapy whereafter remaining tumour cells are treated with telomerase inhibitors. In evaluating the realism of such an approach it is essential to know the effects on telomere status by traditional therapeutic regimens. We have studied the telomere lengths in 47 diagnostic lymphomas and a significant telomere shortening was observed compared to benign lymphoid tissues. In addition, telomere length and telomerase activity were studied in consecutive samples from patients with relapsing non-Hodgkin's lymphomas. Shortened, unchanged and elongated telomere lengths were observed in the relapse samples. The telomere length alterations found in the relapsing lymphomas appeared to be independent of telomerase and rather represented clonal selection random at the telomere length level. These data indicate that anti-telomerase therapy would be suitable in only a fraction of malignant lymphomas.
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