The risk of cardiovascular disease (CVD) after infection is poorly understood.
To determine whether hospitalization for pneumonia is associated with an increased short-term and long-term risk of CVD.
...We examined 2 community-based cohorts: the Cardiovascular Health Study (CHS, n = 5888; enrollment age, ≥65 years; enrollment period, 1989-1994) and the Atherosclerosis Risk in Communities study (ARIC, n = 15,792; enrollment age, 45-64 years; enrollment period, 1987-1989). Participants were followed up through December 31, 2010. We matched each participant hospitalized with pneumonia to 2 controls. Pneumonia cases and controls were followed for occurrence of CVD over 10 years after matching. We estimated hazard ratios (HRs) for CVD at different time intervals, adjusting for demographics, CVD risk factors, subclinical CVD, comorbidities, and functional status.
Hospitalization for pneumonia.
Incident CVD (myocardial infarction, stroke, and fatal coronary heart disease).
Of 591 pneumonia cases in CHS, 206 had CVD events over 10 years after pneumonia hospitalization. CVD risk after pneumonia was highest in the first year. CVD occurred in 54 cases and 6 controls in the first 30 days (HR, 4.07; 95% CI, 2.86-5.27); 11 cases and 9 controls between 31 and 90 days (HR, 2.94; 95% CI, 2.18-3.70); and 22 cases and 55 controls between 91 days and 1 year (HR, 2.10; 95% CI, 1.59-2.60). Additional CVD risk remained elevated into the tenth year, when 4 cases and 12 controls developed CVD (HR, 1.86; 95% CI, 1.18-2.55). In ARIC, of 680 pneumonia cases, 112 had CVD over 10 years after hospitalization. CVD occurred in 4 cases and 3 controls in the first 30 days (HR, 2.38; 95% CI, 1.12-3.63); 4 cases and 0 controls between 31 and 90 days (HR, 2.40; 95% CI, 1.23-3.47); 11 cases and 8 controls between 91 days and 1 year (HR, 2.19; 95% CI, 1.20-3.19); and 8 cases and 7 controls during the second year (HR, 1.88; 95% CI, 1.10-2.66). After the second year, the HRs were no longer statistically significant.
Hospitalization for pneumonia was associated with increased short-term and long-term risk of CVD, suggesting that pneumonia may be a risk factor for CVD.
Subjective cognitive complaints in otherwise normal aging are common but may be associated with preclinical Alzheimer disease in some individuals. Little is known about who is mostly likely to show ...associations between cognitive complaints and preclinical Alzheimer pathology. We sought to demonstrate associations between subjective complaints and brain amyloid-β in cognitively normal older adults; and to explore personality factors as potential moderators of this association.
Cross-sectional observational study.
Clinical neuroimaging research center.
Community volunteer sample of 92 healthy older adults, screened for normal cognition with comprehensive neuropsychological evaluation.
Subjective cognitive self-report measures included the Memory Functioning Questionnaire (MFQ), Cognitive Failures Questionnaire, and the Subjective Cognitive Complaint Scale. Personality was measured with the NEO Five Factor Inventory. Brain amyloid-β deposition was assessed with Pittsburgh compound B (PiB)-PET imaging.
One of three cognitive complaint measures, the MFQ, was associated with global PiB retention (standardized beta = -0.230, p = 0.046, adjusting for age, sex and depressive symptoms). Neuroticism moderated this association such that only high neuroticism individuals showed the predicted pattern of high complaint-high amyloid-β association.
Evidence for association between subjective cognition and brain amyloid-β deposition in healthy older adults is demonstrable but measure-specific. Neuroticism may moderate the MFQ-amyloid-β association such that it is observed in the context of higher trait neuroticism. Subjective cognitive complaints and neuroticism may reflect a common susceptibility toward psychological distress and negative affect, which are in turn risk factors for cognitive decline in aging and incident Alzheimer disease.
The effect of procalcitonin-guided use of antibiotics on treatment for suspected lower respiratory tract infection is unclear.
In 14 U.S. hospitals with high adherence to quality measures for the ...treatment of pneumonia, we provided guidance for clinicians about national clinical practice recommendations for the treatment of lower respiratory tract infections and the interpretation of procalcitonin assays. We then randomly assigned patients who presented to the emergency department with a suspected lower respiratory tract infection and for whom the treating physician was uncertain whether antibiotic therapy was indicated to one of two groups: the procalcitonin group, in which the treating clinicians were provided with real-time initial (and serial, if the patient was hospitalized) procalcitonin assay results and an antibiotic use guideline with graded recommendations based on four tiers of procalcitonin levels, or the usual-care group. We hypothesized that within 30 days after enrollment the total antibiotic-days would be lower - and the percentage of patients with adverse outcomes would not be more than 4.5 percentage points higher - in the procalcitonin group than in the usual-care group.
A total of 1656 patients were included in the final analysis cohort (826 randomly assigned to the procalcitonin group and 830 to the usual-care group), of whom 782 (47.2%) were hospitalized and 984 (59.4%) received antibiotics within 30 days. The treating clinician received procalcitonin assay results for 792 of 826 patients (95.9%) in the procalcitonin group (median time from sample collection to assay result, 77 minutes) and for 18 of 830 patients (2.2%) in the usual-care group. In both groups, the procalcitonin-level tier was associated with the decision to prescribe antibiotics in the emergency department. There was no significant difference between the procalcitonin group and the usual-care group in antibiotic-days (mean, 4.2 and 4.3 days, respectively; difference, -0.05 day; 95% confidence interval CI, -0.6 to 0.5; P=0.87) or the proportion of patients with adverse outcomes (11.7% 96 patients and 13.1% 109 patients; difference, -1.5 percentage points; 95% CI, -4.6 to 1.7; P<0.001 for noninferiority) within 30 days.
The provision of procalcitonin assay results, along with instructions on their interpretation, to emergency department and hospital-based clinicians did not result in less use of antibiotics than did usual care among patients with suspected lower respiratory tract infection. (Funded by the National Institute of General Medical Sciences; ProACT ClinicalTrials.gov number, NCT02130986 .).
In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who ...were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary.
In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support.
We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval CI, 0.82 to 1.31; P=0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support.
In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.).
The risk of cardiovascular events after severe sepsis is not known, and these events may explain increased long-term mortality in survivors of severe sepsis.
To determine whether survivors of severe ...sepsis hospitalization have high long-term risk of cardiovascular events. We examined whether higher risk is due to severe sepsis hospitalization or poor prehospitalization health status, and if the higher risk is also observed in patients hospitalized for infectious and noninfectious reasons, and in other critically ill patients.
Unmatched and matched-cohort analyses of Medicare beneficiaries. For unmatched analysis, we compared patients with severe sepsis admitted to the intensive care unit (ICU) and survived hospitalization (n = 4,179) to unmatched population control subjects (n = 819,283). For matched analysis, we propensity-score-matched each patient with severe sepsis to four control subjects (population, hospitalized, non-severe sepsis ICU control subjects, and infection hospitalization). Primary outcome was 1-year incidence rate of hospitalization for cardiovascular events.
Cardiovascular events were common among patients discharged alive after severe sepsis hospitalization (29.5%; 498.2 events/1,000 person-years). Survivors of severe sepsis had a 13-fold higher risk of cardiovascular events compared with unmatched control subjects (498.2 vs. 36 events/1,000 person-years; P < 0.0001), and a 1.9-fold higher risk compared with matched-population control subjects (P < 0.0001). Survivors of severe sepsis had 1.1-fold higher risk compared with matched hospitalized patients and infection hospitalizations (P = 0.002 and 0.001) and similar risk compared with matched-ICU control subjects.
Survivors of severe sepsis have high risk of cardiovascular events. The higher risk is mainly due to poor prehospitalization health status, and is also seen in a broader population of acutely ill patients.
Despite concern over the appropriateness and quality of care provided in an intensive care unit (ICU) at the end of life, the number of Americans who receive ICU care at the end of life is unknown. ...We sought to describe the use of ICU care at the end of life in the United States using hospital discharge data from 1999 for six states and the National Death Index.
Retrospective analysis of administrative data to calculate age-specific rates of hospitalization with and without ICU use at the end of life, to generate national estimates of end-of-life hospital and ICU use, and to characterize age-specific case mix of ICU decedents.
All nonfederal hospitals in the states of Florida, Massachusetts, New Jersey, New York, Virginia, and Washington.
All inpatients in nonfederal hospitals in the six states in 1999.
None.
We found that there were 552,157 deaths in the six states in 1999, of which 38.3% occurred in hospital and 22.4% occurred after ICU admission. Using these data to project nationwide estimates, 540,000 people die after ICU admission each year. The age-specific rate of ICU use at the end of life was highest for infants (43%), ranged from 18% to 26% among older children and adults, and fell to 14% for those >85 yrs. Average length of stay and costs were 12.9 days and $24,541 for terminal ICU hospitalizations and 8.9 days and $8,548 for non-ICU terminal hospitalizations.
One in five Americans die using ICU services. The doubling of persons over the age of 65 yrs by 2030 will require a system-wide expansion in ICU care for dying patients unless the healthcare system pursues rationing, more effective advanced care planning, and augmented capacity to care for dying patients in other settings.
Objective
We utilized the amyloid imaging ligand Pittsburgh Compound B (PiB) to determine the presence of Alzheimer's disease (AD) pathology in different mild cognitive impairment (MCI) subtypes and ...to relate increased PiB binding to other markers of early AD and longitudinal outcome.
Methods
Twenty‐six patients with MCI (13 single‐domain amnestic‐MCI a‐MCI, 6 multidomain a‐MCI, and 7 nonamnestic MCI) underwent PiB imaging. Twenty‐three had clinical follow‐up (21.2 ± 16.0 standard deviation months) subsequent to their PiB scan.
Results
Using cutoffs established from a control cohort, we found that 14 (54%) patients had increased levels of PiB retention and were considered “amyloid‐positive.” All subtypes were associated with a significant proportion of amyloid‐positive patients (6/13 single‐domain a‐MCI, 5/6 multidomain a‐MCI, 3/7 nonamnestic MCI). There were no obvious differences in the distribution of PiB retention in the nonamnestic MCI group. Predictors of conversion to clinical AD in a‐MCI, including poorer episodic memory, and medial temporal atrophy, were found in the amyloid‐positive relative to amyloid‐negative a‐MCI patients. Longitudinal follow‐up demonstrated 5 of 13 amyloid‐positive patients, but 0 of 10 amyloid‐negative patients, converted to clinical AD. Further, 3 of 10 amyloid‐negative patients “reverted to normal.”
Interpretation
These data support the notion that amyloid‐positive patients are likely to have early AD, and that the use of amyloid imaging may have an important role in determining which patients are likely to benefit from disease‐specific therapies. In addition, our data are consistent with longitudinal studies that suggest a significant percentage of all MCI subtypes will develop AD. Ann Neurol 2009;65:557–568
The present study was designed to document psychiatric disorders among candidates for weight loss surgery and to examine the relationship of psychopathology to degree of obesity and functional health ...status.
The authors collected demographic and clinical information from 288 individuals seeking surgery. Assessments were administered independently of the preoperative screening and approval process. The study group was mostly female (83.3%) and white (88.2%). Mean body mass index (BMI) of the group was 52.2 kg/m(2) (SD=9.7), and the mean age was 46.2 years (SD=9.4).
Approximately 66% of the participants had a lifetime history of at least one axis I disorder, and 38% met diagnostic criteria at the time of preoperative evaluation. In addition, 29% met criteria for one or more axis II disorders. Axis I psychopathology, but not axis II, was positively related to BMI, and both axis I and axis II psychopathology were associated with lower scores on the Medical Outcomes Study 36-item Short-Form Health Survey.
Current and past DSM-IV psychiatric disorders are prevalent among bariatric surgery candidates and are associated with greater obesity and lower functional health status, highlighting the need to understand potential implications for surgery preparation and outcome. Future work also will focus on the course of psychiatric disorder during the post-surgery period and its relationship to weight loss and maintenance.
An important research application of amyloid imaging with positron emission tomography (PET) is detection of the earliest evidence of fibrillar amyloid-beta (Aβ) deposition. Use of amyloid PET for ...this purpose, requires a reproducible method for defining a cutoff that separates individuals with no significant Aβ deposition from those in which Aβ deposition has begun. We previously reported the iterative outlier approach (IO) for the analysis of Pittsburgh Compound-B (PiB) PET data. Developments in amyloid imaging since the initial report of IO have led us to re-examine the generalizability of this method. IO was developed using full-dynamic atrophy-corrected PiB PET data obtained from a group of control subjects with a fairly distinct separation between PiB-positive PiB(+) and PiB-negative PiB(−) subjects.
We tested the performance of IO using late-summed tissue ratio data with atrophy correction or with an automated template method without atrophy correction and tested the robustness of the method when applied to a cohort of older subjects in which separation between PiB(+) and PiB(−) subjects was not so distinct.
The IO method did not perform consistently across analyses and performed particularly poorly when separation was less clear. We found that a sparse k-means (SKM) cluster analysis approach performed significantly better; performing more consistently across methods and subject cohorts. We also compared SKM to a consensus visual read approach and found very good correspondence.
The visual read and SKM methods, applied together, may optimize the identification of early Aβ deposition. These methods have the potential to provide a standard approach to the detection of PiB-positivity that is generalizable across centers.
► Limitations of the iterative outlier method for Aβ-positive cutoffs ► Use of sparse k-means as a method for identification of Aβ-positive cutoffs ► Comparison of the above objective methods to visual reads shows good agreement. ► A combination of methods may be the best approach to identify early Aβ.
Objective Safety culture may influence patient outcomes, but evidence is limited. We sought to determine if intensive care unit (ICU) safety culture is independently associated with outcomes. Design ...Cohort study combining safety culture survey data with the Project IMPACT Critical Care Medicine (PICCM) clinical database. Setting Thirty ICUs participating in the PICCM database. Participants A total of 65 978 patients admitted January 2001–March 2005. Interventions None. Main outcome measures Hospital mortality and length of stay (LOS). Methods From December 2003 to April 2004, we surveyed study ICUs using the Safety Attitudes Questionnaire-ICU version, a validated instrument that assesses safety culture across six factors. We calculated factor mean and percent-positive scores (% respondents with mean score ≥75 on a 0–100 scale) for each ICU, and generated case-mix adjusted, patient-level, ICU-clustered regression analyses to determine the independent association of safety culture and outcome. Results We achieved a 47.9% response (2103 of 4373 ICU personnel). Culture scores were mostly low to moderate and varied across ICUs (range: 13–88, percent-positive scores). After adjustment for patient, hospital and ICU characteristics, for every 10% decrease in ICU perceptions of management percent-positive score, the odds ratio for hospital mortality was 1.24 (95% CI: 1.07–1.44; P = 0.005). For every 10% decrease in ICU safety climate percent-positive score, LOS increased 15% (95% CI: 1−30%; P = 0.03). Sensitivity analyses for non-response bias consistently associated safety climate with outcome, but also yielded some counterintuitive results. Conclusion In a multicenter study conducted in the USA, perceptions of management and safety climate were moderately associated with outcomes. Future work should further develop methods of assessing safety culture and association with outcomes.
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