The formation of clouds affects brown dwarf and planetary atmospheres of nearly all effective temperatures. Iron and silicate condense in L dwarf atmospheres and dissipate at the L/T transition. Minor species such as sulfides and salts condense in mid- to late T dwarfs. For brown dwarfs below T eff 450 K, water condenses in the upper atmosphere to form ice clouds. Currently, over a dozen objects in this temperature range have been discovered, and few previous theoretical studies have addressed the effect of water clouds on brown dwarf or exoplanetary spectra. Here we present a new grid of models that include the effect of water cloud opacity. We find that they become optically thick in objects below T eff 350-375 K. Unlike refractory cloud materials, water-ice particles are significantly nongray absorbers; they predominantly scatter at optical wavelengths through the J band and absorb in the infrared with prominent features, the strongest of which is at 2.8 μm. H2O, NH3, CH4, and H2 CIA are dominant opacity sources; less abundant species may also be detectable, including the alkalis, H2S, and PH3. PH3, which has been detected in Jupiter, is expected to have a strong signature in the mid-infrared at 4.3 μm in Y dwarfs around T eff = 450 K; if disequilibrium chemistry increases the abundance of PH3, it may be detectable over a wider effective temperature range than models predict. We show results incorporating disequilibrium nitrogen and carbon chemistry and predict signatures of low gravity in planetary mass objects. Finally, we make predictions for the observability of Y dwarfs and planets with existing and future instruments, including the James Webb Space Telescope and Gemini Planet Imager. © 2014. The American Astronomical Society. All rights reserved.

Background

Estimation of glomerular filtration rate (GFR) using estimated glomerular filtration rate creatinine (eGFRcr) is central to clinical practice but has limitations. We tested the hypothesis that serum metabolomic profiling can identify novel markers that in combination can provide more accurate GFR estimates.

Methods

We performed a cross-sectional study of 200 African American Study of Kidney Disease and Hypertension (AASK) and 265 Multi-Ethnic Study of Atherosclerosis (MESA) participants with measured GFR (mGFR). Untargeted gas chromatography/dual mass spectrometry- and liquid chromatography/dual mass spectrometry-based quantification was followed by the development of targeted assays for 15 metabolites. On the log scale, GFR was estimated from single- and multiple-metabolite panels and compared with eGFR using the Chronic Kidney Disease Epidemiology equations with creatinine and/or cystatin C using established metrics, including the proportion of errors >30% of mGFR (1-P30), before and after bias correction.

Results

Of untargeted metabolites in the AASK and MESA, 283 of 780 (36%) and 387 of 1447 (27%), respectively, were significantly correlated (P ≤ 0.001) with mGFR. A targeted metabolite panel eGFR developed in the AASK and validated in the MESA was more accurate (1-P30 3.7 and 1.9%, respectively) than eGFRcr [11.2 and 18.5%, respectively (P < 0.001 for both)] and estimating GFR using cystatin C (eGFRcys) [10.6% (P = 0.02) and 9.1% (P < 0.05), respectively] but was not consistently better than eGFR using both creatinine and cystatin C [3.7% (P > 0.05) and 9.1% (P < 0.05), respectively]. A panel excluding creatinine and demographics still performed well [1-P30 6.4% (P = 0.11) and 3.4% (P < 0.001) in the AASK and MESA] versus eGFRcr.

Conclusions

Multimetabolite panels can enable accurate GFR estimation. Metabolomic equations, preferably excluding creatinine and demographic characteristics, should be tested for robustness and generalizability as a potential confirmatory test when eGFRcr is unreliable.

We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial. We compared changes in albumin, body weight, and composition among 245 patients randomized to six or three times per week in-center hemodialysis (Daily Trial) and 87 patients randomized to six times per week nocturnal or three times per week conventional hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial, there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months. There was a significant relative decrease in predialysis body weight of 1.5 ± 0.2 kg in the six times per week group at 1 month, but this significantly rebounded by 1.3 ± 0.5 kg over the remaining 11 months. Extracellular water (ECW) decreased in the six times per week compared with the three per week hemodialysis group. There were no significant between-group differences in phase angle, intracellular water, or body cell mass (BCM). In the Nocturnal Trial, there were no significant between-group differences in any study parameter. Any gain in 'dry' body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant. Thus, frequent in-center hemodialysis reduced ECW but did not increase serum albumin or BCM while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition.

OBJECTIVE To examine variation in antibiotic coverage and detection of resistant pathogens in community-onset pneumonia. DESIGN Cross-sectional study. SETTING A total of 128 hospitals in the Veterans Affairs health system. PARTICIPANTS Hospitalizations with a principal diagnosis of pneumonia from 2009 through 2010. METHODS We examined proportions of hospitalizations with empiric antibiotic coverage for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAER) and with initial detection in blood or respiratory cultures. We compared lowest- versus highest-decile hospitals, and we estimated adjusted probabilities (AP) for patient- and hospital-level factors predicting coverage and detection using hierarchical regression modeling. RESULTS Among 38,473 hospitalizations, empiric coverage varied widely across hospitals (MRSA lowest vs highest, 8.2% vs 42.0%; PAER lowest vs highest, 13.9% vs 44.4%). Detection rates also varied (MRSA lowest vs highest, 0.5% vs 3.6%; PAER lowest vs highest, 0.6% vs 3.7%). Whereas coverage was greatest among patients with recent hospitalizations (AP for anti-MRSA, 54%; AP for anti-PAER, 59%) and long-term care (AP for anti-MRSA, 60%; AP for anti-PAER, 66%), detection was greatest in patients with a previous history of a positive culture (AP for MRSA, 7.9%; AP for PAER, 11.9%) and in hospitals with a high prevalence of the organism in pneumonia (AP for MRSA, 3.9%; AP for PAER, 3.2%). Low hospital complexity and rural setting were strong negative predictors of coverage but not of detection. CONCLUSIONS Hospitals demonstrated widespread variation in both coverage and detection of MRSA and PAER, but probability of coverage correlated poorly with probability of detection. Factors associated with empiric coverage (eg, healthcare exposure) were different from those associated with detection (eg, microbiology history). Providing microbiology data during empiric antibiotic decision making could better align coverage to risk for resistant pathogens and could promote more judicious use of broad-spectrum antibiotics. Infect Control Hosp Epidemiol 2017;38:937-944.

Background

Various indicators of progression of chronic kidney disease (CKD) have been used as outcomes in clinical research studies. The effect of using varying measures on the association of risk factors with CKD progression has not been well characterized.

Study design

Prospective cohort study.

Setting & participants

The Chronic Renal Insufficiency Cohort (CRIC) Study (N=3,939) enrolled men and women with mild to moderate CKD, 48% of whom had diabetes and 42% were self-reported black race.

Predictors

Age, race, sex, diabetes, baseline estimated glomerular filtration rate (eGFR), proteinuria, and other established CKD risk factors.

Outcomes

Death, end-stage renal disease (ESRD), and eGFR events, including: (1) eGFR halving, (2) eGFR<15mL/min/1.73m(2), (3) eGFR halving and <15mL/min/1.73m(2), (4) eGFR decrease of 20mL/min/1.73m(2), (5) eGFR halving or decrease of 20mL/min/1.73m(2), and (6) eGFR decrease of 25% and change in CKD stage.

Results

Mean entry eGFR was 44.9mL/min/1.73m(2). Annual rates of death, ESRD, and eGFR halving were 2.5%, 4.0%, and 6.1%, respectively, during an average follow-up of 5.4 years. Associations between risk factors and ESRD and eGFR events were similar across different definitions. However, these associations were substantially different from those with death. HRs for ESRD, eGFR halving, and death in the highest compared to the lowest proteinuria category were 11.83 (95% CI, 8.40-16.65), 11.19 (95% CI, 8.53-14.68), and 1.47 (95% CI, 1.10-1.96), respectively.

Limitations

Participants may not be representative of the entire CKD population.

Conclusions

Using ESRD or eGFR events, but not death, in the definition of kidney disease outcomes is appropriate in follow-up studies to identify risk factors for CKD progression.

Background

In 2005, pneumonia practice guidelines recommended broad-spectrum antibiotics for patients with risk factors for nosocomial pathogens. The impact of these recommendations on the ability of providers to match treatment with nosocomial pathogens is unknown.

Methods

Among hospitalizations with a principal diagnosis of pneumonia at 128 Department of Veterans Affairs medical centers from 2006 through 2010, we measured annual trends in antibiotic selection; initial blood or respiratory cultures positive for methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Acinetobacter species; and alignment between antibiotic coverage and culture results for MRSA and P. aeruginosa, calculating sensitivity, specificity, and diagnostic odds ratio using a 2 × 2 contingency table.

Results

In 95 511 hospitalizations for pneumonia, initial use of vancomycin increased from 16% in 2006 to 31% in 2010, and piperacillin-tazobactam increased from 16% to 27%, and there was a decrease in both ceftriaxone (from 39% to 33%) and azithromycin (change from 39% to 36%) (P < .001 for all). The proportion of hospitalizations with cultures positive for MRSA decreased (from 2.5% to 2.0%; P < .001); no change was seen for P. aeruginosa (1.9% to 2.0%; P = .14) or Acinetobacter spp. (0.2% to 0.2%; P = .17). For both MRSA and P. aeruginosa, sensitivity increased (from 46% to 65% and 54% to 63%, respectively; P < .001) and specificity decreased (from 85% to 69% and 76% to 68%; P < .001), with no significant changes in diagnostic odds ratio (decreases from 4.6 to 4.1 [P = .57] and 3.7 to 3.2 [P = .95], respectively).

Conclusions

Between 2006 and 2010, we found a substantial increase in the use of broad-spectrum antibiotics for pneumonia despite no increase in nosocomial pathogens. The ability of providers to accurately match antibiotic coverage to nosocomial pathogens remains low.

Importance

Metronidazole hydrochloride has historically been considered first-line therapy for patients with mild to moderate Clostridium difficile infection (CDI) but is inferior to vancomycin hydrochloride for clinical cure. The choice of therapy may likewise have substantial consequences on other downstream outcomes, such as recurrence and mortality, although these secondary outcomes have been less studied.

Objective

To evaluate the risk of recurrence and all-cause 30-day mortality among patients receiving metronidazole or vancomycin for the treatment of mild to moderate and severe CDI.

Design, setting, and participants

This retrospective, propensity-matched cohort study evaluated patients treated for CDI, defined as a positive laboratory test result for the presence of C difficile toxins or toxin genes in a stool sample, in the US Department of Veterans Affairs health care system from January 1, 2005, through December 31, 2012. Data analysis was performed from February 7, 2015, through November 22, 2016.

Exposures

Treatment with vancomycin or metronidazole.

Main outcomes and measures

The outcomes of interest in this study were CDI recurrence and all-cause 30-day mortality. Recurrence was defined as a second positive laboratory test result within 8 weeks of the initial CDI diagnosis. All-cause 30-day mortality was defined as death from any cause within 30 days of the initial CDI diagnosis.

Results

A total of 47 471 patients (mean [SD] age, 68.8 [13.3] years; 1947 women [4.1%] and 45 524 men [95.9%]) developed CDI, were treated with vancomycin or metronidazole, and met criteria for entry into the study. Of 47 147 eligible first treatment episodes, 2068 (4.4%) were with vancomycin. Those 2068 patients were matched to 8069 patients in the metronidazole group for a total of 10 137 included patients. Subcohorts were constructed that comprised 5452 patients with mild to moderate disease and 3130 patients with severe disease. There were no differences in the risk of recurrence between patients treated with vancomycin vs those treated with metronidazole in any of the disease severity cohorts. Among patients in the any severity cohort, those who were treated with vancomycin were less likely to die (adjusted relative risk, 0.86; 95% CI, 0.74 to 0.98; adjusted risk difference, -0.02; 95% CI, -0.03 to -0.01). No significant difference was found in the risk of mortality between treatment groups among patients with mild to moderate CDI, but vancomycin significantly reduced the risk of all-cause 30-day mortality among patients with severe CDI (adjusted relative risk, 0.79; 95% CI, 0.65 to 0.97; adjusted risk difference, -0.04; 95% CI, -0.07 to -0.01).

Conclusions and relevance

Recurrence rates were similar among patients treated with vancomycin and metronidazole. However, the risk of 30-day mortality was significantly reduced among patients who received vancomycin. Our findings may further justify the use of vancomycin as initial therapy for severe CDI.

Background

Despite efforts to reduce antibiotic prescribing for acute respiratory infections (ARIs), information on factors that drive prescribing is limited.

Objective

To examine trends in antibiotic prescribing in the Veterans Affairs population over an 8-year period and to identify patient, provider, and setting sources of variation.

Design

Retrospective, cross-sectional study.

Setting

All emergency departments and primary and urgent care clinics in the Veterans Affairs health system.

Participants

All patient visits between 2005 and 2012 with primary diagnoses of ARIs that typically had low proportions of bacterial infection. Patients with infections or comorbid conditions that indicated antibiotic use were excluded.

Measurements

Overall antibiotic prescription; macrolide prescription; and patient, provider, and setting characteristics extracted from the electronic health record.

Results

The proportion of 1 million visits with ARI diagnoses that resulted in antibiotic prescriptions increased from 67.5% in 2005 to 69.2% in 2012 (P < 0.001). The proportion of macrolide antibiotics prescribed increased from 36.8% to 47.0% (P < 0.001). Antibiotic prescribing was highest for sinusitis (adjusted proportion, 86%) and bronchitis (85%) and varied little according to fever, age, setting, or comorbid conditions. Substantial variation was identified in prescribing at the provider level: The 10% of providers who prescribed the most antibiotics did so during at least 95% of their ARI visits, and the 10% who prescribed the least did so during 40% or fewer of their ARI visits.

Limitation

Some clinical data that may have influenced the prescribing decision were missing.

Conclusion

Veterans with ARIs commonly receive antibiotics, regardless of patient, provider, or setting characteristics. Macrolide use has increased, and substantial variation was identified in antibiotic prescribing at the provider level.

Primary funding source

U.S. Department of Veterans Affairs, Centers for Disease Control and Prevention.

Importance

Use of empirical broad-spectrum antibiotics for pneumonia has increased owing to concern for resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The association of empirical anti-MRSA therapy with outcomes among patients with pneumonia is unknown, even for high-risk patients.

Objective

To compare 30-day mortality among patients hospitalized for pneumonia receiving empirical anti-MRSA therapy vs standard empirical antibiotic regimens.

Design, setting, and participants

Retrospective multicenter cohort study was conducted of all hospitalizations in which patients received either anti-MRSA or standard therapy for community-onset pneumonia in the Veterans Health Administration health care system from January 1, 2008, to December 31, 2013. Subgroups of patients analyzed were those with initial intensive care unit admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Primary analysis was an inverse probability of treatment-weighted propensity score analysis using generalized estimating equation regression; secondary analyses included an instrumental variable analysis. Statistical analysis was conducted from June 14 to November 20, 2019.

Exposures

Empirical anti-MRSA therapy plus standard pneumonia therapy vs standard therapy alone within the first day of hospitalization.

Main outcomes and measures

Risk of 30-day all-cause mortality after adjustment for patient comorbidities, vital signs, and laboratory results. Secondary outcomes included the development of kidney injury and secondary infections with Clostridioides difficile, vancomycin-resistant Enterococcus species, or gram-negative bacilli.

Results

Among 88 605 hospitalized patients (86 851 men; median age, 70 years [interquartile range, 62-81 years]), empirical anti-MRSA therapy was administered to 33 632 (38%); 8929 patients (10%) died within 30 days. Compared with standard therapy alone, in weighted propensity score analysis, empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio [aRR], 1.4 [95% CI, 1.3-1.5]), kidney injury (aRR, 1.4 [95% CI, 1.3-1.5]), and secondary C difficile infections (aRR, 1.6 [95% CI, 1.3-1.9]), vancomycin-resistant Enterococcus spp infections (aRR, 1.6 [95% CI, 1.0-2.3]), and secondary gram-negative rod infections (aRR, 1.5 [95% CI, 1.2-1.8]). Similar associations between anti-MRSA therapy use and 30-day mortality were found by instrumental variable analysis (aRR, 1.6 [95% CI, 1.4-1.9]) and among patients admitted to the intensive care unit (aRR, 1.3 [95% CI, 1.2-1.5]), those with a high risk for MRSA (aRR, 1.2 [95% CI, 1.1-1.4]), and those with MRSA detected on surveillance testing (aRR, 1.6 [95% CI, 1.3-1.9]). No significant favorable association was found between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1 [95% CI, 0.8-1.4]).

Conclusions and relevance

This study suggests that empirical anti-MRSA therapy was not associated with reduced mortality for any group of patients hospitalized for pneumonia. These results contribute to a growing body of evidence that questions the value of empirical use of anti-MRSA therapy using existing risk approaches.

Background

Electronic health records provide the opportunity to assess system-wide quality measures. Veterans Affairs Pharmacy Benefits Management Center for Medication Safety uses medication use evaluation (MUE) through manual review of the electronic health records.

Objective

To compare an electronic MUE approach versus human/manual review for extraction of antibiotic use (choice and duration) and severity metrics.

Research design

Retrospective.

Subjects

Hospitalizations for uncomplicated pneumonia occurring during 2013 at 30 Veterans Affairs facilities.

Measures

We compared summary statistics, individual hospitalization-level agreement, facility-level consistency, and patterns of variation between electronic and manual MUE for initial severity, antibiotic choice, daily clinical stability, and antibiotic duration.

Results

Among 2004 hospitalizations, electronic and manual abstraction methods showed high individual hospitalization-level agreement for initial severity measures (agreement=86%-98%, κ=0.5-0.82), antibiotic choice (agreement=89%-100%, κ=0.70-0.94), and facility-level consistency for empiric antibiotic choice (anti-MRSA r=0.97, P<0.001; antipseudomonal r=0.95, P<0.001) and therapy duration (r=0.77, P<0.001) but lower facility-level consistency for days to clinical stability (r=0.52, P=0.006) or excessive duration of therapy (r=0.55, P=0.005). Both methods identified widespread facility-level variation in antibiotic choice, but we found additional variation in manual estimation of excessive antibiotic duration and initial illness severity.

Conclusions

Electronic and manual MUE agreed well for illness severity, antibiotic choice, and duration of therapy in pneumonia at both the individual and facility levels. Manual MUE showed additional reviewer-level variation in estimation of initial illness severity and excessive antibiotic use. Electronic MUE allows for reliable, scalable tracking of national patterns of antimicrobial use, enabling the examination of system-wide interventions to improve quality.