| 1. |
- Hassan, Amin S, et al.
(författare)
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A Stronger Innate Immune Response During Hyperacute HIV-1 Infection is associated with ACUTE retroviral syndrome
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 73:5, s. 832-841
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute retroviral syndrome (ARS) is associated with HIV-1 subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS.METHODS: Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive from Kenya, Rwanda, Uganda, Zambia and Sweden were analysed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on eleven symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS.RESULTS: Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n=36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% CI: 1.7-28.8], p=0.003). IP-10 was fourteen-fold higher during hAHI, elevated in seven of the eleven symptoms, and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI: 90.3-100.0).CONCLUSIONS: A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.
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| 2. |
- Dong, Yi-Min, et al.
(författare)
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Development and Validation of a Nomogram for Assessing Survival in Patients With COVID-19 Pneumonia
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 72:4, s. 652-660
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Tidskriftsartikel (refereegranskat)abstract
- Background. The outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide and continues to threaten peoples' health as well as put pressure on the accessibility of medical systems. Early prediction of survival of hospitalized patients will help in the clinical management of COVID-19, but a prediction model that is reliable and valid is still lacking. Methods. We retrospectively enrolled 628 confirmed cases of COVID-19 using positive RT-PCR tests for SARS-CoV-2 in Tongji Hospital, Wuhan, China. These patients were randomly grouped into a training (60%) and a validation (40%) cohort. In the training cohort, LASSO regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of patients with COVID-19. A nomogram based on the 3 variables was built for clinical use. AUCs, concordance indexes (C-index), and calibration curves were used to evaluate the efficiency of the nomogram in both training and validation cohorts. Results. Hypertension, higher neutrophil-to-lymphocyte ratio, and increased NT-proBNP values were found to be significantly associated with poorer prognosis in hospitalized patients with COVID-19. The 3 predictors were further used to build a prediction nomogram. The C-indexes of the nomogram in the training and validation cohorts were 0.901 and 0.892, respectively. The AUC in the training cohort was 0.922 for 14-day and 0.919 for 21-day probability of in-hospital survival, while in the validation cohort this was 0.922 and 0.881, respectively. Moreover, the calibration curve for 14- and 21-day survival also showed high coherence between the predicted and actual probability of survival. Conclusions. We built a predictive model and constructed a nomogram for predicting in-hospital survival of patients with COVID-19. This model has good performance and might be utilized clinically in management of COVID-19.
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| 3. |
- Höper, Linnea, et al.
(författare)
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Vasculitis due to Candidatus Neoehrlichia mikurensis : a cohort study of 40 Swedish patients
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:7, s. e2372-e2378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Candidatus (Ca.) Neoehrlichia (N.) mikurensis is an emerging tick-borne pathogen of humans that is closely related to Ehrlichia and Anaplasma species. This strict intracellular bacterium escapes detection by routine microbiologic diagnostic methods such as blood culture leading to considerable under-diagnosis of the infectious disease it causes, neoehrlichiosis.METHODS: Here, we describe the vascular and thromboembolic events afflicting a series of 40 patients diagnosed with neoehrlichiosis in Sweden during a 10-year period (2009-2019).RESULTS: The majority of the patients (60%) developed vascular events ranging from repeated thrombophlebitis, deep vein thrombosis, pulmonary embolism, transitory ischemic attacks to arteritis. Younger age was a risk factor for vascular complications. In contrast, there was no difference in the incidence of vascular events between immunosuppressed and immunocompetent patients. However, there were qualitative differences such that deep vein thrombosis exclusively afflicted the immunosuppressed patients whereas arteritis was restricted to the immunocompetent ones. We also present the case histories of two patients who developed vasculitis mimicking polyarteritis nodosa and giant cell arteritis. Both were cured by doxycycline treatment.CONCLUSIONS: Ca. N. mikurensis infection should be considered in patients living in tick-endemic areas of Europe and northern Asia who present with atypical vascular and/or thromboembolic events. Early diagnosis and antibiotics targeting this emerging infectious agent can eradicate the infection and prevent the development of new vascular events.
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| 4. |
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| 5. |
- Nibell, Olof, et al.
(författare)
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Oral fluoroquinolone use and the risk of acute liver injury: a nationwide cohort study
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838.
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotics are considered to be among the most frequent causes of drug-related acute liver injury (ALI). Although many ALIs have mild and reversible clinical outcomes, there is substantial risk of severe reactions leading to acute liver failure, need for liver transplant, and death. Recent studies have raised concerns of hepatotoxic potential related to the use of fluoroquinolones.MethodsThis study examined the risk of ALI associated with oral fluoroquinolone treatment compared with amoxicillin (419 930 courses, propensity score matched 1:1). The information on drug use was collected from a national, registry-based cohort derived from all Swedish adults aged 40–85 years.ResultsDuring a follow-up period of 60 days, users of oral fluoroquinolones had a >2-fold risk of ALI compared to users of amoxicillin (hazard ratio, 2.32 [95% confidence interval {CI}, 1.01–5.35). The adjusted absolute risk difference for use of fluoroquinolones as compared to amoxicillin was 4.94 (95% CI, .04–16.3) per 1 million episodes.ConclusionsIn this propensity score–matched study, fluoroquinolone treatment was associated with an increased risk of ALI in the first 2 months after starting treatment.
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| 6. |
- Snygg-Martin, Ulrika, 1965, et al.
(författare)
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Cumulative Incidence of Infective Endocarditis in Patients with Congenital Heart Disease: A Nationwide, Case-Control Study Over Nine Decades
- 2021
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Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 73:8, s. 1469-1475
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Congenital heart disease (CHD) is a lifelong predisposing condition for infective endocarditis (IE). As a consequence of advances in pediatric care, the number of adults with CHD is now exceeding the number of children. The goal of the present study was to determine the cumulative incidence of IE in patients with CHD and detect temporal changes compared with controls. METHODS: Nationwide registry-based case-control study of patients with CHD born 1930-2017 matched with 10 random controls. Infective endocarditis episodes were linked using the Swedish 10-digit personal identification number. RESULTS: In total, 89 541 patients with CHD and 890 470 matched controls were included. In patients with CHD, 1477 IE episodes were registered and 447 episodes in controls. Patients with CHD had 8.5% cumulative incidence of IE at age 87 years, compared with 0.7% in matched controls. Incidence rate of IE per 100 000 person-years was 65.5 (95% confidence interval [CI] 62.2-68.9) and 1.8 (95% CI: 1.7-2.0) in CHD patients and controls, respectively. By age 18 years, patients with CHD had an IE incidence similar to that of 81-year-old controls. Incidence of IE differed by age but not by birth year. Bacterial etiology was registered from 1997 in half of the IE episodes; among CHD IE cases, 43.3% were caused by streptococci and 29.8% by Staphylococcus aureus. CONCLUSIONS: Infective endocarditis remains an important complication in patients with CHD. Incidence correlate with age and the number of IE episodes are expected to increase as the CHD population grow older.
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| 7. |
- Stoner, Marie C.D., et al.
(författare)
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Modeling Combination Interventions to Prevent Human Immunodeficiency Virus in Adolescent Girls and Young Women in South Africa (HIV Prevention Trials Network 068)
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:7, s. e1911-e1918
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Combination interventions may be an effective way to prevent human immunodeficiency virus (HIV) in adolescent girls and young women. However, current studies are not designed to understand which specific interventions and combinations will be most effective. We estimate the possible impacts of interventions on a combination of factors associated with HIV.METHODS: We used the g-formula to model interventions on combinations of HIV risk factors to identify those that would prevent the most incident HIV infections, including low school attendance, intimate partner violence, depression, transactional sex, and age-disparate partnerships. We used data from the HIV Prevention Trials Network (HPTN) 068 study in rural South Africa from 2011 to 2017. We estimated HIV incidence under a potential intervention that reduced each risk factor and compared this to HIV incidence under the current distribution of these risk factors.RESULTS: Although many factors had strong associations with HIV, potential intervention estimates did not always suggest large reductions in HIV incidence because the prevalence of risk factors was low. When modeling combination effects, an intervention to increase schooling, decrease depression, and decease transactional sex showed the largest reduction in incident infection (risk difference, -1.4%; 95% confidence interval [CI], -2.7% to -.2%), but an intervention on only transactional sex and depression still reduced HIV incidence by -1.3% (95% CI, -2.6% to -.2%).CONCLUSIONS: To achieve the largest reductions in HIV, both prevalence of the risk factor and strength of association with HIV must be considered. Additionally, intervening on more risk factors may not necessarily result in larger reductions in HIV incidence.
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| 8. |
- Avellan, Sanna, et al.
(författare)
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Adjunctive Corticosteroids for Lyme Neuroborreliosis Peripheral Facial Palsy-A Prospective Study With Historical Controls
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 73:7, s. 1211-1215
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Tidskriftsartikel (refereegranskat)abstract
- Background. Lyme neuroborreliosis peripheral facial palsy (LNB PFP) and idiopathic PFP, Bell's palsy (BP), are the most common causes of facial palsy in borrelia-endemic areas and are clinically similar. Early treatment with corticosteroids has been shown to be effective in Bell's palsy, and antibiotics improve the outcome in LNB. However, there is a lack of knowledge on how the addition of corticosteroids to standard antibiotic treatment affects the outcome in LNB PFP. Methods. This prospective, open trial with historical controls was conducted at 2 large hospitals in western Sweden between 2011 and 2018. Adults who presented with LNB PFP were included in the study group and were treated with oral doxycycline 200 mg twice daily for 10 days and prednisolone 60 mg once daily for 5 days, then tapered over 5 days. The historical controls were adult patients with LNB PFP included in previous studies and treated with oral doxycycline. Both groups underwent a follow-up lumbar puncture and were followed until complete recovery or for 12 months. Results. Fifty-seven patients were included, 27 in the study group and 30 in the control group. Two patients (7%) in the study group and 6 patients (20%) in the control group suffered from sequelae at the end follow-up. There was no statistically significant difference between the groups, either in the proportion of patients with sequelae or in the decline in cerebrospinal fluid mononuclear cell count. Conclusions. Adjunctive corticosteroids neither improve nor impair the outcome for patients with LNB PFP treated with doxycycline.
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| 9. |
- Cresswell, Fiona, V, et al.
(författare)
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High-Dose Oral and Intravenous Rifampicin for the Treatment of Tuberculous Meningitis in Predominantly Human Immunodeficiency Virus (HIV)-Positive Ugandan Adults : A Phase II Open-Label Randomized Controlled Trial
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:5, s. 876-884
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in human immunodeficiency virus (HIV) coinfection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. Methods: In this phase II open-label trial, Ugandan adults with suspected TBM were randomized to standard-of-care control (PO-10, rifampicin 10 mg/kg/day), intravenous rifampicin (IV-20, 20 mg/kg/day), or high-dose oral rifampicin (PO-35, 35 mg/kg/day). We performed PK sampling on days 2 and 14. The primary outcomes were total exposure (AUC(0-24)), maximum concentration (C-max), CSF concentration, and grade 3-5 adverse events. Results: We enrolled 61 adults, 92% were living with HIV, median CD4 count was 50 cells/mu L (interquartile range [IQR] 46-56). On day 2, geometric mean plasma AUC(0-24hr) was 42.9.h mg/L with standard-of-care 10 mg/kg dosing, 249.h mg/L for IV-20 and 327.h mg/L for PO-35 (P<.001). In CSF, standard of care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC(0-24hr) 0.27 mg/L, compared with 1.74 mg/L (95% confidence interval [CI] 1.2-2.5) for IV-20 and 2.17 mg/L (1.6-2.9) for PO-35 regimens (P<.001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (P=.34). Conclusions: Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe and respectively resulted in exposures similar to 6- and similar to 8-fold higher than standard of care, and CSF levels above the MIC.
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| 10. |
- Dong, Yi-Min, et al.
(författare)
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Reply to Collins et al
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:3, s. 558-559
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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