| 1. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
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Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia--case report.
- 2006
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Ingår i: BMC infectious diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since the introduction of HAART the incidence of HIV dementia has declined and HAART seems to improve neurocognitive function in patients with HIV dementia. Currently, HIV dementia develops mainly in patients without effective treatment, though it has also been described in patients on HAART and milder HIV-associated neuropsychological impairment is still frequent among HIV-1 infected patients regardless of HAART. Elevated cerebrospinal fluid (CSF) levels of markers of neural injury and immune activation have been found in HIV dementia, but neither of those, nor CSF HIV-1 RNA levels have been proven useful as diagnostic or prognostic pseudomarkers in HIV dementia. CASE PRESENTATION: We report a case of HIV dementia (MSK stage 3) in a 57 year old antiretroviral naïve man who was introduced on zidovudine, lamivudine and ritonavir boosted indinavir, and followed with consecutive lumbar punctures before and after two and 15 months after initiation of HAART. Improvement of neurocognitive function was paralleled by normalisation of CSF neural markers (NFL, Tau and GFAP) levels and a decline in CSF and serum neopterin and CSF and plasma HIV-1 RNA levels. CONCLUSION: The value of these CSF markers as prognostic pseudomarkers of the effect of HAART on neurocognitive impairment in HIV dementia ought to be evaluated in longitudinal studies.
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| 2. |
- Hagberg, Johan, et al.
(författare)
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Nordic retail research : An introduction
- 2012
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Ingår i: Nordic Retail Research: Emerging Diversity. - : BAS Publishers. - 9789172463110 ; , s. 19-32
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- A presentation of retailing in the Nordic countries together with an introduction to the anthology and the co-authors.
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| 3. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Cerebral palsy in preterm infants: a population-based case-control study of antenatal and intrapartal risk factors.
- 2002
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - 0803-5253. ; 91:8, s. 946-51
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have indicated that foetomaternal infection increases the risk of spastic cerebral palsy (CP) in term infants, whereas this association appears to be less evident in preterm infants. The aim of this study was to analyse infection-related risk factors for spastic CP in preterm infants. A population-based series of preterm infants with spastic CP, 91 very preterm (<32 wk) and 57 moderately preterm (32-36 wk), born in 1983-90, were included and matched with a control group (n = 296). In total, 154 maternal, antenatal and intrapartal variables were retrieved from obstetric records. In the entire group, histological chorioamnionitis/pyelonephritis, long interval between rupture of membranes and birth, admission-delivery interval <4 h and Apgar scores of <7 at 1 min just significantly increased the risk of CP, and Apgar scores of <7 at 5 and 10 min were strongly associated with an increased risk. Abruptio placentae, Apgar scores <7 at 1 min and pathological non-stress test (reason for delivery) were significant risk factors of CP only in the moderately preterm and hemiplegic groups, whereas fever before delivery was a significant risk factor in the very preterm and spastic diplegic groups. Antibiotics during pregnancy was associated with CP only in the spastic diplegic CP group. Conclusion: Antenatal infections marginally increased the risk of CP. Low Apgar score and abruptio placentae were associated with CP, especially in moderately preterm infants with hemiplegic CP.
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| 4. |
- Philipson, Anna, 1978-
(författare)
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Health economic aspects of emotional problems and pain symptoms in childhood and adolescence : Long-term outcomes, efficacy and cost-effectiveness of interventions
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Emotional problems and pain symptoms among children and adolescents are a global public health challenge that imposes a great burden on the individuals affected and on society. Because resources are limited, allocation and prioritization are needed. Health economic analysis can constitute a foundation for such decisions.The overall aim of this thesis is to estimate long-term outcomes associated with adolescent depression and to evaluate interventions for emotional problems and pain symptoms in childhood and adolescence from a health economic perspective. The thesis is based on four papers: paper I is a longitudinal cohort study of 539 participants, showing that adolescent depression is associated with reduced earnings in adulthood, papers II, III, and IV are based on two randomized controlled trials of interventions. In paper II, a dance intervention for 112 adolescent females with internalizing symptoms were evaluated. A cost–utility analysis was performed, indicating that the intervention was costeffective given a willingness-to-pay threshold of USD 50,000 with an incremental cost-effectiveness ratio of USD 3830/quality-adjusted life year. Papers III and IV evaluated a dance and yoga intervention for 121 girls, 9–13 years old, with functional abdominal pain disorders. Paper III showed that the intervention group decreased their abdominal pain more than did the control group. In paper IV, the cost–utility analysis of the trial indicated a negative incremental cost-effectiveness ratio, investigated from a societal perspective, over both one and ten years.In conclusion, this thesis identifies a need for preventive as well as treatment interventions for emotional problems in adolescence, to decrease the prevalence of emotional problems and mitigate negative outcomes. Dance or dance and yoga combined can be effective and cost-effective early treatment interventions for emotional problems and pain symptoms among females in childhood and adolescence. These findings may assist decision-makers in resource allocation within this area
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| 5. |
- Abdulle, Sahra, 1970, et al.
(författare)
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CSF neurofilament protein (NFL) - a marker of active HIV-related neurodegeneration.
- 2007
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 254:8, s. 1026-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND METHODS : The light subunit of the neurofilament protein (NFL), a major structural component of myelinated axons, is a sensitive indicator of axonal injury in the central nervous system (CNS) in a variety of neurodegenerative disorders. Cerebrospinal fluid (CSF) NFL concentrations were measured by ELISA (normal < 250 ng/l) in archived samples from 210 HIV-infected patients not taking antiretroviral treatment: 55 with AIDS dementia complex (ADC), 44 with various CNS opportunistic infections/tumours (CNS OIs), 95 without neurological symptoms or signs, and 16 with primary HIV infection (PHI). The effect of highly active antiretroviral treatment (HAART) was studied by repeated CSF sampling in four of the ADC patients initiating treatment. RESULTS : CSF NFL concentrations were significantly higher in patients with ADC (median 2590 ng/l, IQR 780-7360) and CNS OIs (2315 ng/l, 985-7390 ng/l) than in neuroasymptomatic patients (<250 ng/l, <250-300) or PHI (<250 ng/l, <250-280), p < 0.001. Among patients with ADC, those with more severe disease (stage 2-4) had higher levels than those with milder disease (stage 0.5-1), p < 0.01. CSF NFL declined during HAART to the limit of detection in parallel with virological response and neurological improvement in ADC.CSF NFL concentrations were higher in neuroasymptomatic patients with lower CD4-cell strata than higher, p < 0.001. This increase was less marked than in the ADC patients and noted in 26/58 neuroasymptomatic patients with CD4 counts <200/mul compared to 1/37 with CD4-cells >/=200/mul. CONCLUSIONS : The findings of this study support the value of CSF NFL as a useful marker of ongoing CNS damage in HIV infection. Markedly elevated CSF NFL concentrations in patients without CNS OIs are associated with ADC, follow the grade of severity, and decrease after initiation of effective antiretroviral treatment. Nearly all previously suggested CSF markers of ADC relate to immune activation or HIV viral load that do not directly indicate brain injury. By contrast NFL is a sensitive marker of such injury, and should prove useful in evaluating the presence and activity of ongoing CNS injury in HIV infection.
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| 6. |
- Ahlgren, Erika, et al.
(författare)
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Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.
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| 7. |
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| 8. |
- Alaie, Iman, et al.
(författare)
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Adolescent depression, early psychiatric comorbidities, and adulthood welfare burden : a 25-year longitudinal cohort study
- 2021
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer. - 0933-7954 .- 1433-9285. ; 56:11, s. 1993-2004
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Depression at all ages is recognized as a global public health concern, but less is known about the welfare burden following early-life depression. This study aimed to (1) estimate the magnitude of associations between depression in adolescence and social transfer payments in adulthood; and (2) address the impact of major comorbid psychopathology on these associations.METHODS: This is a longitudinal cohort study of 539 participants assessed at age 16-17 using structured diagnostic interviews. An ongoing 25-year follow-up linked the cohort (n = 321 depressed; n = 218 nondepressed) to nationwide population-based registries. Outcomes included consecutive annual data on social transfer payments due to unemployment, work disability, and public assistance, spanning from age 18 to 40. Parameter estimations used the generalized estimating equations approach.RESULTS: Adolescent depression was associated with all forms of social transfer payments. The estimated overall payment per person and year was 938 USD (95% CI 551-1326) over and above the amount received by nondepressed controls. Persistent depressive disorder was associated with higher recipiency across all outcomes, whereas the pattern of findings was less clear for subthreshold and episodic major depression. Moreover, depressed adolescents presenting with comorbid anxiety and disruptive behavior disorders evidenced particularly high recipiency, exceeding the nondepressed controls with an estimated 1753 USD (95% CI 887-2620).CONCLUSION: Adolescent depression is associated with considerable public expenditures across early-to-middle adulthood, especially for those exposed to chronic/persistent depression and psychiatric comorbidities. This finding suggests that the clinical heterogeneity of early-life depression needs to be considered from a longer-term societal perspective.
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| 9. |
- Alaie, Iman, et al.
(författare)
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Uppsala Longitudinal Adolescent Depression Study (ULADS)
- 2019
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To present the Uppsala Longitudinal Adolescent Depression Study, initiated in Uppsala, Sweden, in the early 1990s. The initial aim of this epidemiological investigation was to study the prevalence, characteristics and correlates of adolescent depression, and has subsequently expanded to include a broad range of social, economic and health-related long-term outcomes and cost-of-illness analyses.Participants: The source population was first-year students (aged 16-17) in upper-secondary schools in Uppsala during 1991-1992, of which 2300 (93%) were screened for depression. Adolescents with positive screening and sex/age-matched peers were invited to a comprehensive assessment. A total of 631 adolescents (78% females) completed this assessment, and 409 subsequently completed a 15year follow-up assessment. At both occasions, extensive information was collected on mental disorders, personality and psychosocial situation. Detailed social, economic and health-related data from 1993 onwards have recently been obtained from the Swedish national registries for 576 of the original participants and an age-matched reference population (N=200 000).Findings to date: The adolescent lifetime prevalence of a major depressive episode was estimated to be 11.4%. Recurrence in young adulthood was reported by the majority, with a particularly poor prognosis for those with a persistent depressive disorder or multiple somatic symptoms. Adolescent depression was also associated with an increased risk of other adversities in adulthood, including additional mental health conditions, low educational attainment and problems related to intimate relationships.Future plans: Longitudinal studies of adolescent depression are rare and must be responsibly managed and utilised. We therefore intend to follow the cohort continuously by means of registries. Currently, the participants are approaching mid-adulthood. At this stage, we are focusing on the overall long-term burden of adolescent depression. For this purpose, the research group has incorporated expertise in health economics. We would also welcome extended collaboration with researchers managing similar datasets.
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| 10. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
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Higher HIV-1 RNA cutoff level required in cerebrospinal fluid than in blood to predict positive HIV-1 isolation
- 2000
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Ingår i: J Med Virol. ; 62:1, s. 9-13
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 can be isolated from the vast majority of blood samples taken from HIV-1-seropositive patients not treated with antiretroviral drugs. Isolation rates from cerebrospinal fluid (CSF) samples are considerably lower, ranging between 20-70%. The objective of this study was to determine the cutoff levels for HIV-1 RNA that would yield a positive predictive value > or =90% for positive virus isolation from CSF and blood. Quantitative HIV-1 RNA PCR (Amplicor HIV monitor, version 1.0, Roche Diagnostic Systems) and virus isolation were used to examine 303 CSF samples and 278 paired blood samples from 157 HIV-1-seropositive patients. Patients on antiretroviral treatment provided 140 of the CSF samples and 131 of the blood samples. CSF samples that were positive by culture numbered 137 of 303 (45%), as compared with 216 of 278 (78%) blood samples. In the case of samples taken from patients with antiretroviral treatment, 28% were positive by culture from CSF and 63% from blood. As expected, mean HIV-1 RNA levels were higher in CSF and blood samples positive by culture than in samples negative by culture. A cutoff level of >5,000 HIV-1 RNA copies/ml was required to yield a positive predictive value for positive virus isolation from CSF samples of > or =90%, whereas the cutoff level for blood samples was just above the detection limit of the assay (>200 HIV-1 copies/ml).
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| 11. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
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Increased blood-brain barrier permeability in neuro-asymptomatic HIV-1-infected individuals--correlation with cerebrospinal fluid HIV-1 RNA and neopterin levels
- 2001
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Ingår i: J Neurovirol. ; 7:6, s. 542-7
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to assess the frequency of blood-brain barrier (BBB) impairment, as measured by the albumin ratio, in neuro-asymptomatic HIV-1-infected individuals without antiretroviral treatment and the correlation between BBB disruption and intrathecal immune activation and HIV-1 RNA levels. Serum and cerebrospinal fluid (CSF) albumin, neopterin, and HIV-1 RNA levels were analysed in 110 neuro-asymptomatic HIV-1-infected individuals at different stages of disease; 63 classified as CDC A, 25 as CDC B, and 22 as CDC C. Increased BBB permeability was found in 17 of 110 (15%) of HIV-1-infected individuals. This proportion was sustained throughout the CDC stages. The albumin ratio was correlated with the CSF neopterin levels (r(s) = 0.36, P < 0.001), the serum neopterin levels (r(s) = 0.37, P < 0.001), and the CSF HIV-1 RNA levels (r(s) = 0.26, P < 0.01), but not with the plasma HIV-1 RNA levels. The correlations between the albumin ratio and the CSF and serum neopterin concentrations and the CSF HIV-1 RNA levels indicate that immune activation and, possibly, intrathecal HIV-1 virus replication are important factors associated with increased BBB permeability in HIV-1 infection.
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| 12. |
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| 13. |
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| 14. |
- Edén, Arvid, 1975, et al.
(författare)
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CSF biomarkers in patients with COVID-19 and neurological symptoms: A case series.
- 2021
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Ingår i: Neurology. - 1526-632X. ; 96:2
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Tidskriftsartikel (refereegranskat)abstract
- To explore whether hospitalized patients with SARS-CoV-2 and neurologic symptoms have evidence of CNS infection, inflammation and injury using CSF biomarker measurements.We assessed CSF SARS-CoV-2 RNA along with CSF biomarkers of intrathecal inflammation (CSF white blood cell count, neopterin, β2-microglobulin (β2M) and immunoglobulin G-index), blood-brain-barrier (BBB) integrity (albumin ratio), and axonal injury (CSF neurofilament light chain protein [NfL]) in 6 patients with moderate to severe COVID-19 and neurologic symptoms who had undergone a diagnostic lumbar puncture. Neurologic symptoms and signs included features of encephalopathies (4/6), suspected meningitis (1/6) and dysgeusia (1/6). SARS-CoV-2 infection was confirmed by rtPCR analysis of nasopharyngeal swabs.SARS-CoV-2 RNA was detected in the plasma of 2 patients (Cycle threshold [Ct] value 35.0-37.0) and in CSF at low levels (Ct 37.2, 38.0, 39.0) in 3 patients in one but not in a second rtPCR assay. CSF neopterin (median, 43.0 nmol/L) and β2-microglobulin (median, 3.1 mg/L) were increased in all. Median IgG-index (0.39), albumin ratio (5.35) and CSF white blood cell count (<3 cells/µL) were normal in all, while CSF NfL was elevated in 2 patients.Our results on patients with COVID-19 and neurologic symptoms suggest an unusual pattern of marked CSF inflammation in which soluble markers were increased but white cell response and other immunologic features typical of CNS viral infections were absent. While our initial hypothesis centered on CNS SARS-CoV-2 invasion, we could not convincingly detect SARS-CoV-2 as the underlying driver of CNS inflammation. These features distinguish COVID-19 CSF from other viral CNS infections, and raise fundamental questions about the CNS pathobiology of SARS-CoV-2 infection.
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| 15. |
- Eriksson, Kerstin Margareta, 1955-, et al.
(författare)
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Quality of life and cost-effectiveness of a 3-year trial of lifestyle intervention in primary health care
- 2010
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Ingår i: Archives of Internal Medicine. - Chicago : American Medical Association. - 0003-9926 .- 1538-3679. ; 170:16, s. 1470-1479
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lifestyle interventions reduce cardiovascular risk and diabetes but reports on long term effects on quality of life (QOL) and health care utilization are rare. The aim was to investigate the impact of a primary health care based lifestyle intervention program on QOL and cost-effectiveness over 3 years.Methods: 151 men and women, age 18-65 yr, at moderate-to-high risk for cardiovascular disease, were randomly assigned to either lifestyle intervention with standard care or standard care alone. Intervention consisted of supervised exercise sessions and diet counseling for 3 months, followed by regular group meetings during 3years. Change in QOL was measured with EuroQol (EQ-5D, EQ VAS), the 36-item Short Form Health Survey (SF-36), and the SF-6D. The health economic evaluation was performed from a societal view and a treatment perspective. In a cost-utility analysis the costs, gained quality-adjusted life years (QALY) and savings in health care were considered. Cost-effectiveness was also described using the Net Monetary Benefit Method.Results: Significant differences between groups over the 3-yr period were shown in EQ VAS, SF-6D and SF-36 physical component summary but not in EQ-5D or SF-36 mental component summary. There was a net saving of 47 USD per participant. Costs per gained QALY, savings not counted, were 1,668 – 4,813 USD. Probabilities of cost-effectiveness were 89 – 100 %, when 50 000 USD was used as stakeholder’s threshold of willingness to pay for a gained QALY.Conclusion: Lifestyle intervention in primary care improves QOL and is highly cost-effective in relation to standard care.
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| 16. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Amyloid and tau cerebrospinal fluid biomarkers in HIV infection.
- 2009
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. METHODS: In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPalpha and sAPPbeta), amyloid beta fragment 1-42 (Abeta1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. RESULTS: CSF sAPPalpha and sAPPbeta concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Abeta1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. CONCLUSIONS: Parallel reductions of CSF sAPPalpha and sAPPbeta in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.
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| 17. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Cerebrospinal fluid signs of neuronal damage after antiretroviral treatment interruption in HIV-1 infection.
- 2005
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Ingår i: AIDS research and therapy. - : Springer Science and Business Media LLC. - 1742-6405. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The neurofilament is a major structural component of myelinated axons. Increased cerebrospinal fluid (CSF) concentrations of the light chain of the neurofilament protein (NFL) can serve as a sensitive indicator of central nervous system (CNS) injury. To assess whether interrupting antiretroviral treatment of HIV infection might have a deleterious effect on the CNS, we measured NFL levels in HIV-infected subjects interrupting therapy. We identified subjects who had CSF HIV RNA concentrations below 50 copies/mL at the time combination antiretroviral therapy was interrupted, and for whom CSF samples were available before and after the interruption. RESULTS: A total of 8 subjects were studied. The median (range) CSF NFL level at baseline was <125 (<125-220) ng/L (normal <250 ng/L). All 8 subjects exhibited an increase in CSF and plasma HIV RNA after stopping therapy, accompanied by intrathecal immunoactivation as evidenced by CSF lymphocytic pleocytosis (7/8 patients) and increased CSF neopterin concentration (5/6 patients). Three subjects showed a consistent increase in CSF NFL, rising from <125 ng/L to a maximum of 880 (at day 148), 1,010 (day 58) and 10,930 ng/L (day 101). None exhibited new neurological symptoms or signs, or experienced functional deterioration during the period off treatment; of 5 who underwent brief quantitative neurological testing, none showed worsening performance. CONCLUSION: These findings suggest that resurgence of active HIV replication may result in measurable, albeit subclinical, CNS injury. Further studies are needed to define the frequency and pathobiological importance of the increase in CSF NFL.
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| 18. |
- Gisslén, Magnus, 1962, et al.
(författare)
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CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
- 2019
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Ingår i: Neurology-Neuroimmunology & Neuroinflammation. - : Ovid Technologies (Wolters Kluwer Health). - 2332-7812. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To explore changes in CSF sTREM2 concentrations in the evolving course of HIV-1 infection. In this retrospective cross-sectional study, we measured concentrations of the macrophage/ microglial activation marker sTREM2 in CSF samples from 121 HIV-1-infected adults and 11 HIV-negative controls and examined their correlations with other CSF and blood biomarkers of infection, inflammation, and neuronal injury. CSF sTREM2 increased with systemic and CNS HIV-1 disease severity, with the highest levels found in patients with HIV-associated dementia (HAD). In untreated HIV-1-infected patients without an HAD diagnosis, levels of CSF sTREM2 increased with decreasing CD4(+) T-cell counts. CSF concentrations of both sTREM2 and the neuronal injury marker neurofilament light protein (NFL) were significantly associated with age. CSF sTREM2 levels were also independently correlated with CSF NFL. Notably, this association was also observed in HIV-negative controls with normal CSF NFL. HIV-infected patients on suppressive antiretroviral treatment had CSF sTREM2 levels comparable to healthy controls. Elevations in CSF sTREM2 levels, an indicator of macrophage/microglial activation, are a common feature of untreated HIV-1 infection that increases with CD4(+) T-cell loss and reaches highest levels in HAD. The strong and independent association between CSF sTREM2 and CSF NFL suggests a linkage between microglial activation and neuronal injury in HIV-1 infection. CSF sTREM2 has the potential of being a useful biomarker of innate CNS immune activation in different stages of untreated and treated HIV-1 infection.
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| 19. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Defining and Evaluating HIV-Related Neurodegenerative Disease and Its Treatment Targets: A Combinatorial Approach to Use of Cerebrospinal Fluid Molecular Biomarkers
- 2007
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Ingår i: Journal of NeuroImmune Pharmacology. - : Springer Science and Business Media LLC. - 1557-1890 .- 1557-1904. ; 2:1, s. 112-119
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Tidskriftsartikel (refereegranskat)abstract
- There are a number of reasons that the accomplishments of clinical trials related to HIV-related neurodegenerative disease (HRND) and the AIDS dementia complex (ADC) have had such limited impact on clinical practice. These include: rapid evolution and progress in the treatment of systemic HIV infection that has quickly outpaced neurological efforts and has markedly reduced disease incidence; ethical constraints that (rightly) demand neurologically compromised patients receive the best available treatment before experimental therapeutics; complicated backgrounds and comorbidities of patients now most susceptible to HRND; and reluctance of general AIDS clinicians and drug companies to look beyond systemic or pivotal outcomes. However, the field has also been slow to adopt methods that better exploit advances in understanding of the pathogenesis of central nervous system (CNS) infection and brain injury, and that might circumvent some of these constraints. Using a simple model of pathogenesis, we propose an approach to characterizing patients, selecting treatment targets, and evaluating outcomes that emphasize a combination of cerebrospinal fluid (CSF) markers. This model begins by using three markers related to cardinal components of HRND: CNS HIV infection (measurement of CSF HIV RNA), intrathecal immunoactivation (CSF neopterin), and brain injury [CSF light chain neurofilament (NFL)]. Careful analysis of this and other marker combinations promises more rational trial design and more rapid progress in managing CNS HIV infection and HRND using both antiviral and adjuvant treatment approaches.
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| 20. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Elevated cerebrospinal fluid neurofilament light protein concentrations predict the development of AIDS dementia complex.
- 2007
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 195:12, s. 1774-8
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Tidskriftsartikel (refereegranskat)abstract
- The light subunit of neurofilament protein (NFL) is a sensitive indicator of central nervous system axonal injury. We retrospectively identified 9 subjects participating in a longitudinal cohort study who developed acquired immunodeficiency syndrome dementia complex (ADC) and who had had a lumbar puncture performed within 2 years before presentation. Elevated cerebrospinal fluid (CSF) NFL concentrations were found in 7 (78%) of the 9 case patients who later developed ADC, compared with 9 (33%) of 27 CD4 cell count-matched HIV-1-infected control subjects. By contrast, no differences were found in CSF HIV-1 RNA or neopterin concentrations between the 2 groups. CSF NFL may prove to be a useful predictive marker for ADC.
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| 21. |
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| 22. |
- Hagberg, Lars A, et al.
(författare)
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Cost-effectiveness of healthcare-based interventions aimed at improving physical activity.
- 2006
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 34:6, s. 641-653
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This article aims to review current knowledge concerning the cost-effectiveness of healthcare-based interventions aimed at improving physical activity. Method: A search was performed for economic evaluations containing the terms ``physical activity'', ``exercise'', or ``fitness''. Cost-effectiveness for the articles found was described based on a model for evaluating interventions intended to promote physical activity. Results: A total of 26 articles were found in the search. Nine of them concern a general population, 7 evaluated older people, and 10 studied disease-specific populations. A preventive perspective is most common, but some have a treatment perspective. Around 20 of the interventions studied were cost-effective according to their authors, but all analyses had some shortcomings in their evaluation methods. Conclusion: This review found many examples of cost-effective interventions. There is a lack of evidence for the cost-effectiveness of interventions aimed at those whose only risk factor for illness is a sedentary lifestyle. There is more evidence, although it is limited, for the cost-effectiveness of interventions aimed at high-risk groups or those who manifest poor health related to physical inactivity. Most of the evidence for cost-effectiveness is for older people and those with heart failure. Promotion of physical activity can be cost-effective with different methods and in different settings, but there remains a lack of evidence for specific methods in specific populations.
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| 23. |
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| 24. |
- Hagberg, Lars Axel, et al.
(författare)
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Measuring the time costs of exercise : a proposed measuring method and a pilot study
- 2010
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Ingår i: Cost Effectiveness and Resource Allocation. - : BioMed Central (BMC). - 1478-7547. ; 8, s. 9-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The cost of time spent on exercise is an important factor in societal-perspective health economic analyses of interventions aimed at promoting physical activity. However, there are no existing measuring methods for estimating time costs. The aim of this article is to describe a way to measure the costs of time spent on physical activity. We propose a model for measuring these time costs, and present the results of a pilot study applying this model to different groups of exercisers.Methods: We began this investigation by developing a model for measuring the time spent on exercise, based on the most important theoretical frameworks for valuing time. In the model, the value of utility in anticipation (expected health benefits) of performing exercise is expressed in terms of health-related quality of life. With this approach, the cost of the time spent on exercise is defined as the value of utility in use of leisure activity forgone minus the value of utility in use of exercise. Utility in use for exercise is valued in comparison with utility in use for leisure activity forgone and utility in use for work.To put the model into practice, we developed a questionnaire with the aim of investigating the valuations made by exercisers, and applied this questionnaire among more experienced and less experienced exercisers.Results: Less experienced exercisers valued the time spent on exercise as being equal to 26% of net wages, while more experienced exercisers valued this time at 7% of net wages (p < 0.001). The higher time costs seen among the less experienced exercisers correlated to a less positive experience of exercise and a more positive experience of the lost leisure activity. There was a significant inverse correlation between the costs of time spent on exercise, and the frequency and duration of regular exercise.Conclusion: The time spent on exercise is an important factor in interventions aimed at promoting physical activity, and should be taken into consideration in cost-effectiveness analyses. The proposed model for measuring the costs of the time spent on exercise seems to be a better method than the previously-used assumptions of time costs.
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| 25. |
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| 26. |
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| 27. |
- Hagberg, Lars, 1956-
(författare)
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Cost-effectiveness of the promotion of physical activity in health care
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction Physical inactivity is a major cause of reduced quality of life, as well as many common diseases and even premature death. Most people, globally, are scarcely or rarely physically active. Consequently, physical inactivity influences the burden of disease, and increases its societal costs. In view of this, it is necessary to ask how health care should respond when the population and the patients are either inactive or rarely physically active. Cost-effectiveness analyses of the promotion of physical activity in health care can contribute substantially to health care policy. Aims The overall aim of this thesis was to investigate the cost-effectiveness of physical activity promotion in the health care system. The specific aims were: (I) to provide a model for analyzing cost-effectiveness and equity in health for community-promoted physical activity, (II) to review current knowledge about the cost-effectiveness of health care based interventions aimed at improving physical activity, (III) to evaluate the cost effectiveness of physical activity promotion as a treatment method in primary health care, (IV) to illustrate the importance of enjoyment of exercise in interventions aimed at promoting physical activity, and (V) to describe a method of valuing the time spent on exercise. Methods Standard methods for economic evaluation were studied and adapted to create a model for the evaluation of physical activity promotion (I). Relevant databases were searched for published articles, and the articles found were analyzed using this economic evaluation model (II). A trial in primary health care was evaluated in a cost-utility analysis based on the model (III). In the same trial, the association between time spent on exercise and enjoyment of exercise was analyzed (IV). A model for valuing the time spent on exercise was developed based on existing approaches to the valuation of time, and used in two different groups of exercisers; experienced and inexperienced (V). Results An economic evaluation model was developed, as was a model to calculate an intervention’s effect on equity in health (I). In total, 26 articles were found regarding the cost-effectiveness of physical activity promotion in health care, and 20 of these described interventions, which the authors considered to be cost-effective (II). The treatment of patients in primary health care by the promotion of physical activity was shown to be cost-effective (III). For the same group of patients, time spent on exercise was associated with enjoyment of exercise (IV). A model for valuing the time spent on exercise was developed and used. Time costs were significantly higher among inexperienced exercisers (V). Conclusions There are many examples of interventions promoting physical activity that may be regarded as cost-effective. In general, it seems to be cost effective to promote physical activity among patients with increased risk, or who manifest poor health associated with physical inactivity. Unfortunately, there is still little evidence of when physical activity should be used, or what the best design of such an intervention might be. Although there is still a need for stronger evidence, the Swedish health care system should use the promotion of physical activity as a standard method among the following patients: • those who manifest increased risk (such as high blood pressure) of ill health due to a physically inactive lifestyle; • frail older people, especially those with increased risk of fall injuries; • those requiring rehabilitation after heart failure.
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| 28. |
- Hagberg, Lars, 1951, et al.
(författare)
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Intrathecal immune activation is associated with cerebrospinal fluid markers of neuronal destruction in AIDS patients
- 2000
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Ingår i: J Neuroimmunol. ; 102:1, s. 51-5
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Tidskriftsartikel (refereegranskat)abstract
- We analysed the relationship between cerebrospinal fluid (CSF) concentrations of the light subunit of the neurofilament protein (NFL, a marker of neurons, mainly axons), neopterin (a marker of immune activation), and quantitative HIV RNA levels in 47 patients with HIV-1 infection, 25 of whom had AIDS. In the AIDS patients, the mean levels of CSF NFL were high indicating neuronal destruction. The CSF NFL and the CSF neopterin concentrations were correlated in the subgroup of patients without CNS opportunistic infection (p < 0.05). There was no significant correlation between NFL and HIV RNA levels in CSF. In HIV seropositive patients without AIDS, only 3/22 had CSF NFL concentrations above the upper normal reference value. The results suggest that CNS neuronal destruction occurs frequently in patients with AIDS but rarely in those without AIDS, and that immune activation rather than the HIV viral load is associated with neurochemical signs of axonal destruction.
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| 29. |
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| 30. |
- Hagberg, Lars, 1956-, et al.
(författare)
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What is the time cost of exercise? Cost of time spent on exercise in a primary health care intervention to increase physical activity
- 2020
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Ingår i: Cost Effectiveness and Resource Allocation. - : Springer Science and Business Media LLC. - 1478-7547. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background In health care interventions aimed at increased physical activity, the individual's time spent on exercise is a substantial input. Time costs should therefore be considered in cost-effectiveness analyses. The aim of this study was to estimate the cost of time spent on exercise among 333 primary health care patients with metabolic risk factors receiving physical activity on prescription. Methods Based on a theoretical framework, a yardstick was constructed with experience of work (representing claim of salary as compensation) as the lower anchor-point, and experience of leisure activity forgone due to extended exercise time (no claim) as the higher anchor-point. Using this yardstick experience of exercise can be valued. Another yardstick was constructed with experience of cleaning at home in combination with willingness to pay for cleaning as the lowest anchor-point. Results The estimated costs of exercise time were between 14 and 37% of net wages, with physical activity level being the most important factor in determining the cost. Among sedentary individuals, the time cost was 21-51% of net wages while among individuals performing regular exercise it was 2-10%. When estimating the cost of time spent on exercise in a cost-effectiveness analysis, experience of exercise, work, leisure activity forgone, and cleaning at home (or other household work that may be relevant to purchase) should be measured. The individual's willingness to pay for cleaning at home and their net salary should also be measured. Conclusions When using a single valuation of cost of time spent on exercise in health care interventions, for employed participants 15-30% of net salary should be used. Among unemployed individuals, lower cost estimation should be applied. Better precision in cost estimations can be achieved if participants are stratified by physical activity levels. Trial registration The study was conducted as a survey of existing clinical physical activity on prescription work, and was approved by the Regional Ethical Review Board in Gothenburg, Sweden (ref: 678-14)
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| 31. |
- Hagberg, Thomas, et al.
(författare)
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How costly was the crisis in Finland and Sweden?
- 2009
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Ingår i: The Great Financial Crisis in Finland and Sweden : The Nordic Experience of Financial Liberalization - The Nordic Experience of Financial Liberalization. - 978 1 84844 305 1 - 978 1 84980 213 0 ; , s. 158-180
-
Bokkapitel (refereegranskat)
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| 32. |
- Hellström, Vivan, et al.
(författare)
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Malignancies in transplanted patients : Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation - experiences from a prospective, clinical, observational study
- 2016
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Ingår i: Acta Oncologica. - Uppsala : Acta Universitatis Upsaliensis. - 0284-186X .- 1651-226X. ; 55:6, s. 774-781
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Tidskriftsartikel (refereegranskat)abstract
- Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post-transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial.Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564).Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p=0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines.Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post-transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers.
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| 33. |
- Krut, Jan Jessen, et al.
(författare)
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Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method.With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.
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| 34. |
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| 35. |
- Mellgren, Åsa, 1973, et al.
(författare)
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Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection
- 2007
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Ingår i: Neurology. ; 69:15, s. 1536-41
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Increased levels of the light-chain neurofilament protein (NFL) in CSF provide a marker of CNS injury in several neurodegenerative disorders and have been reported in the AIDS dementia complex (ADC). We examined the effects of highly active antiretroviral treatment (HAART) on CSF NFL in HIV-1-infected subjects with and without ADC who underwent repeated lumbar punctures (LPs). METHOD: NFL was measured by ELISA (normal reference value < 250 ng/L) in archived CSF samples from 53 patients who had undergone LPs before and after initiation of HAART. RESULTS: Twenty-one of the subjects had increased CSF NFL at baseline, with a median level of 780 ng/L and an intraquartile range (IQR) of 480 to 7300. After 3 months of treatment, NFL concentrations had fallen to normal in 48% (10/21), and the median decreased to 340 ng/L (IQR < 250 to 4070) (p < 0.001), whereas at 1 year, only 4 of 16 of the 21 subjects observed for this length still had elevated NFL levels. Thirty-two subjects had normal NFL at baseline, and all but one remained normal at follow-up. These effects on CSF NFL were seen in association with clinical improvement in ADC patients, decreases in plasma and CSF HIV-1 RNA and CSF neopterin, and increases in blood CD4 T cell counts. CONCLUSION: HAART seems to halt the neurodegenerative process(es) caused by HIV-1, as shown by the significant decrease in CSF NFL after treatment initiation. CSF NFL may serve as a useful marker in monitoring CNS injury in HIV-1 infection and in evaluating CNS efficacy of antiretroviral therapy.
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| 36. |
- Månsdotter, Anna, et al.
(författare)
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Towards capability-adjusted life years in public health and social welfare : results from a Swedish survey on ranking capabilities
- 2020
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Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The aim of this study was to rank capabilities and suggest a relevant set of capabilities for the Swedish context to inform the development of capability-adjusted life years (CALYs). CALYs is a quality of life measure for policy making based on the capability approach by Amartya Sen.MATERIALS AND METHODS: A Swedish governmental review proposed the following 10 relevant capabilities: time, financial situation, mental/physical health, political resources, knowledge, living environment, occupation, social relations, security, and housing. Researchers in health-related disciplines from 5 universities ranked these capabilities from 1 to 10 (most to least important) in a web-based cross-sectional survey; 115 of 171 responses were eligible.RESULTS: Health, social relations, and financial situation were deemed most important. Stratification by gender, research field, and age group revealed few differences. We found that it was possible to rank capabilities and that health, social relations, and financial situation were ranked highest by a non-representative sample of researchers and doctoral students from health-related disciplines at five Swedish universities.CONCLUSIONS: The revealed ranking is dependent on the metric and must be further explored. The findings support continued development of CALYs for monitoring and evaluating outcomes in public health and social-welfare interventions.
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| 37. |
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| 38. |
- Nayeri, Fariba, 1958-, et al.
(författare)
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Hepatocyte Growth Factor Levels in Cerebrospinal Fluid : A Comparison between Acute Bacterial and Nonbacterial Meningitis
- 2000
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 181:6, s. 2092-2094
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Tidskriftsartikel (refereegranskat)abstract
- The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinal fluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P < .001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis.
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| 39. |
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| 40. |
- Nilsson, Magnus, et al.
(författare)
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A 9-band WCDMA/EDGE transceiver supporting HSPA evolution
- 2011
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Ingår i: [Host publication title missing]. - 0193-6530. ; , s. 366-368
-
Konferensbidrag (refereegranskat)abstract
- The future of cellular radio ICs lies in the integration of an ever-increasing number of bands and channel bandwidths. This paper presents a transceiver together with the associated discrete front-end components. The transceiver supports 4 EDGE bands and 9 WCDMA bands (l-VI and Vlll-X), while the radio can be configured to simultaneously support the 4 EDGE bands and up to 5 WCDMA bands: 3 high bands (HB) and 2 low bands (LB). The RX is a SAW-less homodyne composed of a main RX and a diversity RX. To reduce package complexity with so many bands, we chose to minimize the number of ports by using single-ended RF interfaces for both RX and TX. This saves seve ral package pins, but requires careful attention to grounding. The main RX has 8 LNA ports and the diversity RX has 5, with some LNAs supporting multiple bands. On the TX side, 2 ports are used for all EDGE bands and 4 for the WCDMA bands.
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| 41. |
- Nordling Nilson, Linda, 1947, et al.
(författare)
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Dose-related cognitive deficits among floor layers with previous heavy exposure to solvents.
- 2003
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Ingår i: Archives of environmental health. - 0003-9896. ; 58:4, s. 208-17
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Tidskriftsartikel (refereegranskat)abstract
- The authors used tests of attention and memory, which are sensitive to the influence of aging, to explore possible adverse effects on cognitive functioning following past heavy exposure to solvent-based glues, with special reference to dose-effect relationships and interactions with the aging process. The study included 41 floor layers and 40 carpenters (referents) who participated in a longitudinal follow-up assessment. The authors assessed cognitive functioning with the following tests: trail-making, color words, and word recall. Higher cumulative exposure was associated with poorer test performance that was related to concept shifting, episodic memory, and speed of congruent and incongruent color naming. The magnitude of the decrements in memory tasks was equivalent to about 20 yr of age-related decline. Dose-effect relationships were seen mainly for contact adhesives, and there was partial evidence for an interaction between exposure and aging.
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| 42. |
- Philipson, Anna, 1978-, et al.
(författare)
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The cost-effectiveness of a dance and yoga intervention for girls with functional abdominal pain disorders
- 2023
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Ingår i: PharmacoEconomics - Open. - : Springer Nature. - 2509-4262 .- 2509-4254. ; 7, s. 321-335
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Tidskriftsartikel (refereegranskat)abstract
- Background: Functional abdominal pain disorders (FAPDs) affect children worldwide, being more prevalent among girls. The individual and societal burdens of the disease are substantial, and evidence-based interventions are needed. Non-pharmacological treatments have generally produced promising results, with dance and yoga specifically having potential as an effective treatment option. Beside efficacy, the cost-effectiveness of interventions is important when prioritizing and allocating public resources.Objective: This study evaluated the cost-effectiveness of an 8-month dance and yoga intervention for girls with functional abdominal pain or irritable bowel syndrome, based on a randomized control trial called ‘Just in TIME’.Methods: The intervention, performed in Sweden, was studied using a decision analysis tool, i.e., a decision tree within the trial followed by a Markov model with a time horizon of 10 years. The base case considered healthcare costs as well as productivity losses, measuring the effects in gained quality-adjusted life-years (QALYs) and presenting an incremental cost-effectiveness ratio (ICER).Results: The base case results show that the intervention, compared with current practice, was the dominant strategy from both the 12-month and long-term perspectives. The sensitivity analyses indicated that the long-term, but not the short-term, findings were robust for different assumptions and changes in parameter estimates, resulting in ICERs similar to those of the base case scenario.Conclusions: Offering dance and yoga to young girls with FAPDs generates small QALY gains and monetary savings compared with standard healthcare and is likely cost-effective. These findings make a valuable contribution to an area where evidence-based and cost-effective treatment interventions are needed.Clinical Trials Registration Number: ClinicalTrials.gov identifier: NCT02920268; Name: Just in TIME—Intervention With Dance and Yoga for Girls With Recurrent Abdominal Pain
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| 43. |
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| 44. |
- Rosén, Christoffer, 1986, et al.
(författare)
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Cerebrospinal fluid biomarkers in cardiac arrest survivors.
- 2014
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 85:2, s. 227-232
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the levels of various cerebrospinal fluid (CSF) biomarkers related to neuronal damage, inflammation and amyloid β (Aβ) metabolism in patients resuscitated after an out-of-hospital cardiac arrest (CA).
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| 45. |
- Sköldenberg, Birgit, et al.
(författare)
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Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults.
- 2006
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 253:2, s. 163-70
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. METHODS: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). RESULTS: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. CONCLUSION: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.
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| 46. |
- Ssegonja, Richard, et al.
(författare)
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Depressive disorders in adolescence, recurrence in early adulthood, and healthcare usage in mid-adulthood : A longitudinal cost-of-illness study
- 2019
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Ingår i: Journal of Affective Disorders. - : ELSEVIER. - 0165-0327 .- 1573-2517. ; 258, s. 33-41
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Tidskriftsartikel (refereegranskat)abstract
- Background: Depression in adolescence is associated with increased healthcare consumption in adulthood, but prior research has not recognized the heterogeneity of depressive disorders. This paper investigated the additional healthcare usage and related costs in mid-adulthood for individuals with adolescent depression, and examined the mediating role of subsequent depression in early adulthood.Methods: This study was based on the Uppsala Longitudinal Adolescent Depression Study, initiated in Sweden in the early 1990s. Depressive disorders were assessed in adolescence (age 16-17) and early adulthood (age 19-30). Healthcare usage and related costs in mid-adulthood (age 31-40) were estimated using nationwide population-based registries. Participants with specific subtypes of adolescent depression (n = 306) were compared with matched non-depressed peers (n = 213).Results: Women with persistent depressive disorder (PDD) in adolescence utilized significantly more healthcare resources in mid-adulthood. The association was not limited to psychiatric care, and remained after adjustment for individual and parental characteristics. The total additional annual cost for a single age group of females with a history of PDD at a population level was estimated at 3.10 million USD. Depression recurrence in early adulthood mediated the added costs for psychiatric care, but not for somatic care.Limitations: Primary health care data were not available, presumably resulting in an underestimation of the true healthcare consumption. Estimates for males had limited precision due to a relatively small male proportion.Conclusions: On a population level, the additional healthcare costs incurred in mid-adulthood in females with a history of adolescent PDD are considerable. Early treatment and prevention should be prioritized.
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| 47. |
- Tillander, Jonatan, 1975, et al.
(författare)
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Osseointegrated titanium implants for limb prostheses attachments: infectious complications.
- 2010
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Ingår i: Clinical orthopaedics and related research. - : Ovid Technologies (Wolters Kluwer Health). - 1528-1132 .- 0009-921X. ; 468:10, s. 2781-2788
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The concept of osseointegration involves direct contact between titanium implant and bone. This transcutaneous prosthetic system for amputees is intended to assure stable long-term fixation. Most metal transcutaneous implants have failed, primarily owing to infection. QUESTIONS/PURPOSES: We determined the frequency and describe the presentation of infectious complications with this novel method. We also evaluated the bacterial flora at the skin-penetration area and its relation to the development of local and implant-related infection. PATIENTS AND METHODS: We prospectively followed 39 patients with arm and leg amputations fitted with transcutaneous osseointegrated titanium implants a mean of 56 months earlier (range, 132-133 months). There were 33 femoral, one tibial, four ulnar, four radial, and three humeral implants. Patients were selected during a 6-month period in 2005 and identically reevaluated after 3 years. Implant infection was defined as definite, probable, or possible based on clinical, radiologic, and microbiologic evidence. RESULTS: The frequency of implant infection was 5% at inclusion and 18% at followup. One patient with infection recovered owing to antibiotic treatment and another patient had the implant removed. Most implant infections had low infectious activity, and in five of the seven patients with infections, prosthetic use was not affected. The most common bacteria in superficial and deep cultures were Staphylococcus aureus and coagulase-negative staphylococci. CONCLUSIONS: Despite frequent colonization around the skin-implant interface by potentially virulent bacteria such as Staphylococcus aureus and bacteria associated with biomedical device infections such as coagulase-negative staphylococci, this titanium implant system for bone-anchored prostheses caused few infections leading to disability or implant removal. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
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| 48. |
- Tillander, Jonatan, 1975, et al.
(författare)
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Osteomyelitis Risk in Patients With Transfemoral Amputations Treated With Osseointegration Prostheses.
- 2017
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Ingår i: Clinical orthopaedics and related research. - : Ovid Technologies (Wolters Kluwer Health). - 1528-1132 .- 0009-921X. ; 475:12, s. 3100-3108
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Tidskriftsartikel (refereegranskat)abstract
- Percutaneous anchoring of femoral amputation prostheses using osseointegrating titanium implants has been in use for more than 25years. The method offers considerable advantages in daily life compared with conventional socket prostheses, however long-term success might be jeopardized by implant-associated infection, especially osteomyelitis, but the long-term risk of this complication is unknown.(1) To quantify the risk of osteomyelitis, (2) to characterize the clinical effect of osteomyelitis (including risk of implant extraction and impairments to function), and (3) to determine whether common patient factors (age, sex, body weight, diabetes, and implant component replacements) are associated with osteomyelitis in patients with transfemoral amputations treated with osseointegrated titanium implants.We retrospectively analyzed our first 96 patients receiving femoral implants (102 implants; mean implant time, 95months) treated at our center between 1990 and 2010 for osteomyelitis. Six patients were lost to followup. The reason for amputation was tumor, trauma, or ischemia in 97 limbs and infection in five. All patients were referred from other orthopaedic centers owing to difficulty with use or to be fitted with socket prostheses. If found ineligible for this implant procedure no other treatment was offered at our center. Osteomyelitis was diagnosed by medical chart review of clinical signs, tissue culture results, and plain radiographic findings. Proportion of daily prosthetic use when osteomyelitis was diagnosed was semiquantitatively graded as 1 to 3. Survivorship free from implant- associated osteomyelitis and extraction attributable to osteomyelitis respectively was calculated using the Kaplan-Meier estimator. Indication for extraction was infection not responsive to conservative treatment with or without minor débridement or loosening of implant.Implant-associated osteomyelitis was diagnosed in 16 patients corresponding to a 10-year cumulative risk of 20% (95% CI 0.12-0.33). Ten implants were extracted owing to osteomyelitis, with a 10-year cumulative risk of 9% (95% CI 0.04-0.20). Prosthetic use was temporarily impaired in four of the six patients with infection who did not undergo implant extraction. With the numbers available, we did not identify any association between age, BMI, or diabetes with osteomyelitis; however, this study was underpowered on this endpoint.The increased risk of infection with time calls for numerous measures. First, patients should be made aware of the long-term risks, and the surgical team should have a heightened suspicion in patients with method-specific presentation of possible infection. Second, several research questions have been raised. Will the surgical procedure, rehabilitation, and general care standardization since the start of the program result in lower infection rates? Will improved diagnostics and early treatment resolve infection and prevent subsequent extraction? Although not supported in this study, it is important to know if most infections arise as continuous bacterial invasion from the skin and implant interface and if so, how this can be prevented?Level IV, therapeutic study.
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| 49. |
- Tyrberg, Erika, et al.
(författare)
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The effect of vitamin B supplementation on neuronal injury in people living with HIV: a randomized controlled trial
- 2022
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Effective antiretroviral therapy has radically changed the course of the HIV pandemic. However, despite efficient therapy, milder forms of neurocognitive symptoms are still present in people living with HIV. Plasma homocysteine is a marker of vitamin B deficiency and has been associated with cognitive impairment. People living with HIV have higher homocysteine concentrations than HIV-negative controls, and we have previously found an association between plasma homocysteine concentration and CSF concentration of neurofilament light protein, a sensitive marker for ongoing neuronal injury in HIV. This prompted us to perform this randomized controlled trial, to evaluate the effect of vitamin B supplementation on neuronal injury in a cohort of people living with HIV on stable antiretroviral therapy. At the Department of Infectious Diseases at Sahlgrenska University Hospital in Gothenburg, Sweden, 124 virally suppressed people living with HIV were screened to determine eligibility for this study. Sixty-one fulfilled the inclusion criteria by having plasma homocysteine levels at or above 12 mu mol/l. They were randomized (1:1) to either active treatment (with cyanocobalamin 0.5 mg, folic acid 0.8 mg and pyridoxine 3.0 mg) q.d. or to a control arm with a cross over to active treatment after 12 months. Cognitive function was measured repeatedly during the trial, which ran for 24 months. We found a significant correlation between plasma neurofilament light protein and plasma homocysteine at screening (n = 124, r = 0.35, P < 0.0001). Plasma homocysteine levels decreased by 35% from a geometric mean of 15.7 mu mol/l (95% confidence interval 14.7-16.7) to 10.3 mu mol/l (95% confidence interval 9.3-11.3) in the active treatment arm between baseline and Month 12. No significant change was detected in the control arm during the same time period [geometric mean 15.2 (95% confidence interval 14.3-16.2) versus geometric mean 16.5 mu mol/l (95% confidence interval 14.7-18.6)]. A significant difference in change in plasma homocysteine levels was seen between arms at 12 months [-40% (95% confidence interval -48 to -30%), P < 0.001]. However, no difference between arms was seen in either plasma neurofilament light protein levels [-6.5% (-20 to 9%), P = 0.39], or cognitive measures [-0.08 (-0.33 to 0.17), P = 0.53]. Our results do not support a vitamin B-dependent cause of the correlation between neurofilament light protein and homocysteine. Additional studies are needed to further elucidate this matter. Tyrberg et al. report the results of a randomized controlled trial investigating the effect of vitamin B supplementation on neuronal injury in people living with HIV with effective antiretroviral therapy. Supplementation decreased levels of homocysteine but not neuronal injury measured by neurofilament light protein.
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| 50. |
- Wennerås, Christine, 1963, et al.
(författare)
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Distinct Inflammatory Mediator Patterns Characterize Infectious and Sterile Systemic Inflammation in Febrile Neutropenic Hematology Patients
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Invasive infections and sterile tissue damage can both give rise to systemic inflammation with fever and production of inflammatory mediators. This makes it difficult to diagnose infections in patients who are already inflamed, e.g. due to cell and tissue damage. For example, fever in patients with hematological malignancies may depend on infection, lysis of malignant cells, and/or chemotherapy-induced mucosal damage. We hypothesized that it would be possible to distinguish patterns of inflammatory mediators characterizing infectious and non-infectious causes of inflammation, respectively. Analysis of a broad range of parameters using a multivariate method of pattern recognition was done for this purpose. Methods: In this prospective study, febrile (>38 degrees C) neutropenic patients (n = 42) with hematologic malignancies were classified as having or not having a microbiologically defined infection by an infectious disease specialist. In parallel, blood was analyzed for 116 biomarkers, and 23 clinical variables were recorded for each patient. Using O-PLS (orthogonal projection to latent structures), a model was constructed based on these 139 variables that could separate the infected from the non-infected patients. Non-discriminatory variables were discarded until a final model was reached. Finally, the capacity of this model to accurately classify a validation set of febrile neutropenic patients (n = 10) as infected or non-infected was tested. Results: A model that could segregate infected from non-infected patients was achieved based on discrete differences in the levels of 40 variables. These variables included acute phase proteins, cytokines, measures of coagulation, metabolism, organ stress and iron turn-over. The model correctly identified the infectious status of nine out of ten subsequently recruited febrile neutropenic hematology patients. Conclusions: It is possible to separate patients with infectious inflammation from those with sterile inflammation based on inflammatory mediator patterns. This strategy could be developed into a decision-making tool for diverse clinical applications.
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