Ingvild Dalen

Increased severity and mortality in adults co-infected with malaria and HIV in Maputo, Mozambique: a prospective cross-sectional study.

Background Co-infection with falciparum malaria and HIV-1 increases the severity and mortality of both infections in unstable malaria-transmission areas. In contrast, in stable transmission areas, HIV co-infection increases the severity of both infections but has not been found to influence malaria mortality. Methods In a prospective cross-sectional study, clinical and laboratory data were consecutively collected for all adults admitted with fever and/or suspected malaria to the medical department of the Central Hospital of Maputo, Mozambique, during two malaria seasons from January 2011. Malaria and HIV PCRs were performed, and risk factors for fatal outcomes were analysed. The impact of HIV on the clinical presentation and mortality of malaria was assessed. Findings A total of 212 non-pregnant adults with fever and/or suspected malaria and 56 healthy controls were included in the study. Of the 131 patients with confirmed falciparum malaria, 70 were co-infected with HIV-1. The in-hospital mortality of the co-infected patients was 13.0% (9/69) compared with 1.7% (1/59) in the patients without HIV (pu200a=u200a0.018). Malaria severity (pu200a=u200a0.016) and co-infection with HIV (pu200a=u200a0.064) were independent risk factors for death although the association with HIV did not reach statistical significance. The co-infected patients had significantly more frequent respiratory distress, bleeding disturbances, hypoglycaemia, liver and renal failure and high malaria parasitemia compared with the patients with malaria alone. Interpretations HIV co-infection is associated with increased disease severity in and mortality from malaria in an area of stable malaria transmission. This finding was not observed earlier and should motivate doctors working in malaria-endemic areas to consider early HIV testing and a closer follow-up of patients with malaria and HIV co-infection.

The long-term development of non-motor problems after STN-DBS.

Stimulation of the subthalamic nucleus (STN‐DBS) is an established treatment with long‐term beneficial effects on motor symptoms in patients with Parkinsons disease (PD). The long‐term development of non‐motor problems after STN‐DBS is not fully understood. In this study, we have studied how non‐motor problems develop in patients with and without STN‐DBS.

Loss of Dopamine Transporter Binding and Clinical Symptoms in Dementia With Lewy Bodies

Little is known about the underlying mechanisms of clinical symptoms in dementia with Lewy bodies. The aim of this study was to explore the association between loss of striatal dopamine transporter binding and symptoms in dementia with Lewy bodies.

Pelvic girdle pain 3–6 months after delivery in an unselected cohort of Norwegian women

PurposePersistent pelvic girdle pain (PGP) after delivery is considered uncommon. The aim of this study was to assess the frequency of persistent PGP after delivery in an unselected population, its influence on the women’s daily life, and potential risk factors.MethodsThe study population was drawn from a previous retrospective study of pelvic pain (PP) during pregnancy. The women were followed until 3–6xa0months after delivery in a prospective cohort study. All women were contacted by telephone and those with persistent PP were invited to fill in questionnaires and undergo a clinical examination.Results68 of 330 women reported persistent pain in the pelvic area 3–6xa0months after delivery. 47 underwent a clinical examination, after which 36 women were diagnosed with either PGP alone (nxa0=xa025), or PGP combined with low back pain (LBP) (nxa0=xa011). Affected women reported a poor subjective health status, but the pain did not have a major impact on their daily life activities. Women with 3 independent risk factors: age ≥30xa0years, a moderate or high Oswestry Disability Index in pregnancy, and combined PP and LBP during pregnancy, had a 27-fold increased risk for persistent PGP compared with women without these risk factors.Conclusion16xa0% of women that reported PP during pregnancy were found to have persistent PGP 3–6xa0months after the delivery. Women with risk factors for persistent PGP should be identified while pregnant, and offered a follow-up examination 3xa0months after delivery.

Complement Activation Correlates With Disease Severity and Contributes to Cytokine Responses in Plasmodium falciparum Malaria

The impact of complement activation and its possible relation to cytokine responses during malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum malaria and in human whole-blood specimens stimulated with malaria-relevant agents ex vivo. Complement was significantly activated in the malaria cohort, compared with healthy controls, and was positively correlated with disease severity and with certain cytokines, in particular interleukin 8 (IL-8)/CXCL8. This was confirmed in ex vivo-stimulated blood specimens, in which complement inhibition significantly reduced IL-8/CXCL8 release. P. falciparum malaria is associated with systemic complement activation and complement-dependent release of inflammatory cytokines, of which IL-8/CXCL8 is particularly prominent.

Reproducibility and prognostic value of WHO1973 and WHO2004 grading systems in TaT1 urothelial carcinoma of the urinary bladder.

Background European treatment guidelines of TaT1 urinary bladder urothelial carcinomas depend highly on stage and WHO1973-grade but grading reproducibility is wanting. The newer WHO2004 grading system is still debated and both systems are currently used. Aims To compare reproducibility and prognostic value (of stage progression) of the WHO1973 and WHO2004. Methods One hundred and ninety-three primary urothelial carcinomas were reviewed. Follow-up data were retrieved from the patient records. Kappa statistics and Harrells C-index were used. Results Median follow-up was 75 months (range 1–127). 17 patients (9%) progressed, 82% of these within and 18% after 60 months. The distribution of WHO73-grades 1, 2 and 3 was 23%, 51% and 26%, interobserver agreement for each individual grade was 66% (kappau200a=u200a0.68), while for grades 1&2 versus 3 89% (kappau200a=u200a0.68). Intraobserver reproducibility was 68–63% for WHO73 and 88–89% for WHO73 as 1&2 vs.3. Progression free survival rates at 5 years were 95% (grade 1), 98% (grade 2) and 82% (grade 3) and 96% and 82% for grades 1&2 versus 3 (Hazard Ratio, HR, 5.4, pu200a=u200a0.003). Using WHO2004, 62% were low grade and 38% high grade, inter-observer agreement 87% (kappau200a=u200a0.70), intraobserver reproducibility 93%, and progression free 5-year survival rates 97% and 85% (HR 6.6, pu200a=u200a0.004). Positive and negative predictive values for stage progression within 5 years for the WHO73 (1&2 vs. 3) were 18% and 96%, and 15% and 97% for the WHO04. Using Harrells C-index, none of the grading systems was prognostically superior. Conclusion None of the grading systems is prognostically stronger than the others. Most importantly, inter-observer reproducibility and sensitivities for stage progression of both systems are low and need improvement for optimal treatment.

Effect of Vascular Risk Factors on the Progression of Mild Alzheimer's Disease and Lewy Body Dementia

BACKGROUNDnVascular risk factors (VRF) are associated with an increased risk of neurodegenerative disease.nnnOBJECTIVEnTo examine the association between VRF and cognitive decline in patients with Alzheimers disease (AD) and Lewy body dementia (LBD).nnnMETHODSnWe included consecutive referrals with mild AD or LBD to dementia clinics in western Norway from 2005 to 2013. The Mini-Mental Status Exam (MMSE) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) were administered at baseline and then annually for up to five years. The VRF include diabetes mellitus, hypertension, hypercholesterolemia, overweight and smoking. Generalized Estimating Equations (GEE) were used to examine the potential association between VRF scores and the change in MMSE and CDR-SB scores, adjusting for age, sex, and the apolipoprotein ɛ4 allele (APOE4).nnnRESULTSnA total of 200 patients were included (113 AD, 87 LBD) (mean age 76 years, mean baseline MMSE 24.0, mean follow-up time 3.5 years). Smoking was the only VRF significantly associated with a more rapid cognitive decline, however only in the AD group. Being overweight at baseline was associated with a slower cognitive decline. Moreover, hypertension at baseline predicted a slower decline in MMSE scores. In the LBD group diabetes mellitus was found to be associated with a slower increase in CDR-SB scores.nnnCONCLUSIONnWith the exception of smoking, VRF at time of dementia diagnosis were not associated with a more rapid cognitive decline.

Prognostic comparison of proliferation markers and World Health Organization 1973/2004 grades in urothelial carcinomas of the urinary bladder ☆

European treatment guidelines of non-muscle-invasive urothelial carcinoma of the urinary bladder are strongly dependent on grade, but grading reproducibility is wanting. Protocolized proliferation features such as Mitotic Activity Index (MAI), Ki-67, and phosphohistone H3 are prognostic and reproducible. The objective of this population-based study was to compare proliferation biomarkers with each other and with World Health Organization (WHO) 1973/2004 grades with regard to prediction of stage progression. A total of 193 primary non-muscle-invasive urothelial carcinomas were analyzed using WHO73/04 grades and measurement of the proliferation markers mentioned above. Sensitivities, specificities, and positive and negative predictive values with confidence intervals (CIs) were estimated with regard to progression prediction. Kaplan-Meier survival curves were made, and the hazard ratio and Harrells C-index with 95% CIs, P values, and adjusted C-index for stage progression or not of WHO73, WHO04, and the proliferation markers were calculated. The median follow-up time was 75 months (range, 1-127). A total of 111 patients (52%) experienced recurrence within 5 years, and 14 patients (7%) progressed. High values of MAI predicted stage progression with a positive predictive value of 0.22 (95% CI, 0.12-0.37). The positive predictive value of Ki-67 and phosphohistone H3 were 0.15 (both 95% CIs, 0.07-0.29) and comparable to that of the WHO04. The prognostic value of MAI was strongest, exceeding that of the other proliferation markers and the WHO grading systems. In conclusion, in non-muscle-invasive urinary bladder urothelial carcinomas, proliferation biomarkers have prognostic value, possibly exceeding that of the WHO classifications.

Long-Term Mortality and Its Risk Factors in Stroke Survivors

BACKGROUNDnStroke is one of the leading causes of mortality worldwide. Understanding the risk factors associated with stroke mortality is important to improve patient management. Few studies have examined long-term mortality and its associated predictive risk factors.nnnMETHODSnWe examined long-term mortality in 1137 patients with acute stroke and compared it to a geographically age- and sex-matched, stroke-free control group. We followed the stroke patients for as long as 16.4 years. In 1018 of these patients we assessed the effect of demographic, clinical, and hematological factors on mortality.nnnRESULTSnAt the end of the study period, 51.7% of the patients and 32.7% of the stroke-free control individuals had died (hazard ratio 2.2, confidence interval 1.9-2.5, Pu2009<u2009.001). A total of 72.5% of the patients and 53% of the controls with 12 years follow-up (nu2009=u2009570) had died (Pu2009<u2009.001). Regression analyses indicate that, in addition to known risk factors such as age, diabetes, and stroke severity, both low cholesterol (Pu2009<u2009.001) and hemoglobin (Pu2009<u2009.002), hyperhomocysteinemia (Pu2009=u2009.005), and elevated serum creatinine (Pu2009<u2009.001) at index stroke are associated with increased long-term mortality.nnnCONCLUSIONSnStroke patients surviving the first year after stroke have a markedly increased mortality rate as seen in long-term follow-up. Furthermore, the results from this study indicate that changes in creatinine, homocysteine, and hemoglobin should be followed more carefully as standard practice after acute stroke.

Cytokine network in adults with falciparum malaria and HIV-1: increased IL-8 and IP-10 levels are associated with disease severity

Background Co-infection with malaria and HIV increases the severity and mortality of both diseases, but the cytokine responses related to this co-infection are only partially characterised. The aim of this study was to explore cytokine responses in relation to severity and mortality in malaria patients with and without HIV co-infection. Methods This was a prospective cross-sectional study. Clinical data and blood samples were collected from adults in Mozambique. Plasma was analysed for 21 classical pro- and anti-inflammatory cytokines, including interleukins, interferons, and chemokines. Results We included 212 in-patients with fever and/or suspected malaria and 56 healthy controls. Falciparum malaria was diagnosed in 131 patients, of whom 70 were co-infected with HIV-1. The malaria patients had marked increases in their cytokine responses compared with the healthy controls. Some of these changes, particularly interleukin 8 (IL-8) and interferon-γ-inducing protein 10 (IP-10) were strongly associated with falciparum malaria and disease severity. Both these chemokines were markedly increased in patients with falciparum malaria as compared with healthy controls, and raised levels of IL-8 and IP-10 were associated with increased disease severity, even after adjusting for relevant confounders. For IL-8, particularly high levels were found in malaria patients that were co-infected with HIV and in those who died during hospitalization. Interpretations Our findings underscore the complex role of inflammation during infection with P. falciparum, and suggest a potential pathogenic role for IL-8 and IP-10. However, the correlations do not necessarily mean any causal relationship, and further both clinical and mechanistic research is necessary to elucidate the role of cytokines in pathogenesis and protection during falciparum malaria.