Impact of immunosuppressive agents on clinical manifestations and outcome of staphylococcus aureus bloodstream infection: a propensity score-matched analysis in 2 large, prospectively evaluated cohorts

BACKGROUND: Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. METHODS: Data from 2 large prospective, international, multicenter cohort studies (Invasive Staphylococcus aureus Infections Cohort [INSTINCT] and International Staphylococcus aureus Collaboration [ISAC]) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score-matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroid monotherapy and immunosuppressive agents other than steroids [IMOTS]). RESULTS: Of 3188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 nonimmunosuppressed patients. After propensity score matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the 2 groups (death during follow-up: 105/309 [33.9%] immunosuppressed vs 94/309 [30.4%] nonimmunosuppressed; hazard ratio [HR], 1.20 [95% confidence interval {CI}, .84-1.71]). Competing risk analysis showed a cause-specific HR of 1.81 (95% CI, .85-3.87) for SAB-related late complications in patients receiving immunosuppressive agents. The cause-specific HR was higher in patients taking IMOTS (3.69 [95% CI, 1.41-9.68]). CONCLUSIONS: Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTS warrants further investigations

Long-term air pollution, noise, and structural measures of the Default Mode Network in the brain: Results from the 1000BRAINS cohort

BackgroundWhile evidence suggests that long-term air pollution (AP) and noise may adversely affect cognitive function, little is known about whether environmental exposures also promote structural changes in underlying brain networks. We therefore investigated the associations between AP, traffic noise, and structural measures of the Default Mode Network (DMN), a functional brain network known to undergo specific changes with age.MethodsWe analyzed data from 579 participants (mean age at imaging: 66.5 years) of the German 1000BRAINS study. Long-term residential exposure to particulate matter (diameter ≤10 μm [PM10]; diameter ≤2.5 μm [PM2.5]), PM2.5 absorbance (PM2.5abs), nitrogen dioxide (NO2), and accumulation mode particulate number concentration (PNAM) was estimated using validated land use regression and chemistry transport models. Long-term outdoor traffic noise was modeled at participants' homes based on a European Union's Environmental Noise Directive. As measures of brain structure, cortical thickness and local gyrification index (lGI) values were calculated for DMN regions from T1-weighted structural brain images collected between 2011 and 2015. Associations between environmental exposures and brain structure measures were estimated using linear regression models, adjusting for demographic and lifestyle characteristics.ResultsAP exposures were below European Union standards but above World Health Organization guidelines (e.g., PM10 mean: 27.5 μg/m3). A third of participants experienced outdoor 24-h noise above European recommendations. Exposures were not consistently associated with lGI values in the DMN. We observed weak inverse associations between AP and cortical thickness in the right anterior DMN (e.g., −0.010 mm [-0.022, 0.002] per 0.3 unit increase in PM2.5abs) and lateral part of the posterior DMN.ConclusionLong-term AP and noise were not consistently associated with structural parameters of the DMN in the brain. While weak associations were present between AP exposure and cortical thinning of right hemispheric DMN regions, it remains unclear whether AP might influence DMN brain structure in a similar way as aging

Association between Long-Term Air Pollution, Chronic Traffic Noise, and Resting-State Functional Connectivity in the 1000BRAINS Study

BACKGROUND: Older adults show a high variability in cognitive performance that cannot be explained by aging alone. Although research has linked air pollution and noise to cognitive impairment and structural brain alterations, the potential impact of air pollution and noise on functional brain organization is unknown. OBJECTIVE: This study examined the associations between long-term air pollution and traffic noise with measures of functional brain organization in older adults. We hypothesize that exposures to high air pollution and noise levels are associated with age-like changes in functional brain organization, shown by less segregated brain networks. METHODS: Data from 574 participants (44.1% female, 56–85 years of age) in the German 1000BRAINS study (2011–2015) were analyzed. Exposure to particulate matter ([Formula: see text] , [Formula: see text] , and [Formula: see text] absorbance), accumulation mode particle number ([Formula: see text]), and nitrogen dioxide ([Formula: see text]) was estimated applying land-use regression and chemistry transport models. Noise exposures were assessed as weighted 24-h ([Formula: see text]) and nighttime ([Formula: see text]) means. Functional brain organization of seven established brain networks (visual, sensorimotor, dorsal and ventral attention, limbic, frontoparietal and default network) was assessed using resting-state functional brain imaging data. To assess functional brain organization, we determined the degree of segregation between networks by comparing the strength of functional connections within and between networks. We estimated associations between air pollution and noise exposure with network segregation, applying multiple linear regression models adjusted for age, sex, socioeconomic status, and lifestyle variables. RESULTS: Overall, small associations of high exposures with lesser segregated networks were visible. For the sensorimotor networks, we observed small associations between high air pollution and noise and lower network segregation, which had a similar effect size as a 1-y increase in age [e.g., in sensorimotor network, [Formula: see text] (95% CI: [Formula: see text] , 0.009) per 0.3 [Formula: see text] increase in [Formula: see text] absorbance and [Formula: see text] (95% CI: [Formula: see text] , [Formula: see text]) per 1-y age increase]. CONCLUSION: High exposure to air pollution and noise was associated with less segregated functional brain networks. https://doi.org/10.1289/EHP973

Impact of Immunosuppressive Agents on Clinical Manifestations and Outcome of Staphylococcus aureus Bloodstream Infection: A Propensity Score-Matched Analysis in 2 Large, Prospectively Evaluated Cohorts

Background. Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. Methods. Data from 2 large prospective, international, multicenter cohort studies (Invasive Staphylococcus aureus Infections Cohort [INSTINCT] and International Staphylococcus aureus Collaboration [ISAC]) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score-matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroid monotherapy and immunosuppressive agents other than steroids [IMOTS]). Results. Of 3188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 nonimmunosuppressed patients. After propensity score matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the 2 groups (death during follow-up: 105/309 [33.9%] immunosuppressed vs 94/309 [30.4%] nonimmunosuppressed; hazard ratio [HR], 1.20 [95% confidence interval {CI}, .84-1.71]). Competing risk analysis showed a cause-specific HR of 1.81 (95% CI,.85-3.87) for SAB-related late complications in patients receiving immunosuppressive agents. The cause-specific HR was higher in patients taking IMOTS (3.69 [95% CI, 1.41-9.68]). Conclusions. Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTS warrants further investigations

Impact of neutropenia on clinical manifestations and outcome of Staphylococcus aureus bloodstream infection: a propensity score-based overlap weight analysis in two large, prospectively evaluated cohorts

Objectives: This study aimed to investigate whether neutropenia influenced mortality and long-term outcomes of Staphylococcus aureus bloodstream (SAB) infection. Methods: Data from two prospective, multicentre cohort studies (INSTINCT and ISAC) conducted at 20 tertiary care hospitals in six countries between 2006 and 2015 were analyzed. Neutropenic and severely neutropenic patients (defined by proxy of total white blood cell count <1000/μl and <500/μl, respectively, at onset of SAB infection) were compared with a control group using a propensity score model and overlapping weights to adjust for baseline characteristics. Overall survival and time to SAB infection-related late complications (SAB infection recurrence, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed with Cox regression and competing risk analyses, respectively. Results: Of the 3187 included patients, 102 were neutropenic and 70 severely neutropenic at the time of SAB infection onset. Applying overlap weights yielded two groups of 83 neutropenic and 220 nonneutropenic patients, respectively. The baseline characteristics of these groups were exactly balanced. In the Cox regression analysis, we observed no significant difference in survival between the two groups (death during follow up: 36.1% in neutropenic vs. 30.6% in nonneutropenic patients; hazard ratio (HR): 1.21; 95% CI, 0.79–1.83). This finding remained unchanged when we considered severely neutropenic patients (HR: 1.08; 95% CI, 0.60–1.94). A competing risk analysis showed a cause-specific HR of 0.39 (95% CI, 0.11–1.39) for SAB infection-related late complications in neutropenic patients. Discussion: Neutropenia was not associated with a higher survival rate during follow up. The lower rate of SAB infection-related late complications in neutropenic patients should be validated in other cohorts