Risk of postpartum readmission after hypertensive disorder of pregnancy and variation by discharge antihypertensive medication prescription.

BACKGROUND: Patients with hypertensive disorders of pregnancy have a high rate of postpartum readmission. OBJECTIVE: This study aimed to evaluate whether the type of antihypertensive medication prescribed at discharge was associated with postpartum readmission after a hypertensive disorder of pregnancy. STUDY DESIGN: This was a retrospective cohort study of 57,254 pregnancies complicated by hypertensive disorders of pregnancy between 2012 and 2018 in the electronic obstetrical database of Kaiser Permanente Northern California. Postpartum readmissions occurred within 6 weeks after discharge from delivery hospitalization. Cox regression models were used to evaluate the association between the type of antihypertensive medication prescription at discharge (none, labetalol only, nifedipine only, or 2 or more antihypertensive medications) and postpartum readmission, adjusted for type of hypertensive disorder of pregnancy, final inpatient systolic and diastolic blood pressures, age, body mass index, mode of delivery, insurance status, race and ethnicity, delivery facility, comorbidity score, smoking, preterm delivery, parity, and Neighborhood Deprivation Index. RESULTS: Among eligible patients with a hypertensive disorder of pregnancy, 1696 (3.0%) were readmitted within 6 weeks. Approximately 86% of patients were discharged without a prescription for antihypertensive medication; among those discharged with a prescription for antihypertensive medication, most were prescribed either labetalol only (54%) or nifedipine only (30%). The unadjusted readmission risk was the highest for patients discharged with a prescription for labetalol only (7.6%), lower for those discharged with a prescription for nifedipine only (3.6%) or 2 or more antihypertensive medications (3.2%), and the lowest for those discharged without a prescription for antihypertensive medication (2.5%). In the adjusted models, compared with discharge without a prescription for antihypertensive medication, discharge with a prescription for labetalol only was associated with a 63% (hazard ratio, 1.63; 95% confidence interval, 1.41-1.88) greater incidence of postpartum readmission, and discharge with a prescription for nifedipine only and discharge with a prescription for 2 or more antihypertensive medications were associated with 26% (hazard ratio, 0.74; 95% confidence interval, 0.59-0.93) and 47% (hazard ratio, 0.53; 95% confidence interval, 0.38-0.74) lower incidence of postpartum readmission, respectively. There was no strong evidence to suggest that the effect of the type of antihypertensive medication at discharge on the incidence of readmission varied by race and ethnicity (interaction P=.88). The results indicating an elevated risk associated with labetalol use were consistent in models that excluded patients with prepregnancy hypertension. CONCLUSION: Discharge with a prescription for nifedipine alone or multiple antihypertensive medications (vs no medication) was associated with a lower incidence of readmission, whereas discharge with a prescription for labetalol alone was associated with an elevated readmission incidence. A large-scale, prospective research to compare the effectiveness of commonly prescribed hypertension medications at discharge is warranted.

The Gut Microbiome Modulates Body Temperature Both in Sepsis and Health.

Rationale: Among patients with sepsis, variation in temperature trajectories predicts clinical outcomes. In healthy individuals, normal body temperature is variable and has decreased consistently since the 1860s. The biologic underpinnings of this temperature variation in disease and health are unknown. Objectives: To establish and interrogate the role of the gut microbiome in calibrating body temperature. Methods: We performed a series of translational analyses and experiments to determine whether and how variation in gut microbiota explains variation in body temperature in sepsis and in health. We studied patient temperature trajectories using electronic medical record data. We characterized gut microbiota in hospitalized patients using 16S ribosomal RNA gene sequencing. We modeled sepsis using intraperitoneal LPS in mice and modulated the microbiome using antibiotics, germ-free, and gnotobiotic animals. Measurements and Main Results: Consistent with prior work, we identified four temperature trajectories in patients hospitalized with sepsis that predicted clinical outcomes. In a separate cohort of 116 hospitalized patients, we found that the composition of patients' gut microbiota at admission predicted their temperature trajectories. Compared with conventional mice, germ-free mice had reduced temperature loss during experimental sepsis. Among conventional mice, heterogeneity of temperature response in sepsis was strongly explained by variation in gut microbiota. Healthy germ-free and antibiotic-treated mice both had lower basal body temperatures compared with control animals. The Lachnospiraceae family was consistently associated with temperature trajectories in hospitalized patients, experimental sepsis, and antibiotic-treated mice. Conclusions: The gut microbiome is a key modulator of body temperature variation in both health and critical illness and is thus a major, understudied target for modulating physiologic heterogeneity in sepsis.

In critically ill patients, anti-anaerobic antibiotics increase risk of adverse clinical outcomes.

BACKGROUND: Critically ill patients routinely receive antibiotics with activity against anaerobic gut bacteria. However, in other disease states and animal models, gut anaerobes are protective against pneumonia, organ failure and mortality. We therefore designed a translational series of analyses and experiments to determine the effects of anti-anaerobic antibiotics on the risk of adverse clinical outcomes among critically ill patients. METHODS: We conducted a retrospective single-centre cohort study of 3032 critically ill patients, comparing patients who did and did not receive early anti-anaerobic antibiotics. We compared intensive care unit outcomes (ventilator-associated pneumonia (VAP)-free survival, infection-free survival and overall survival) in all patients and changes in gut microbiota in a subcohort of 116 patients. In murine models, we studied the effects of anaerobe depletion in infectious (Klebsiella pneumoniae and Staphylococcus aureus pneumonia) and noninfectious (hyperoxia) injury models. RESULTS: Early administration of anti-anaerobic antibiotics was associated with decreased VAP-free survival (hazard ratio (HR) 1.24, 95% CI 1.06-1.45), infection-free survival (HR 1.22, 95% CI 1.09-1.38) and overall survival (HR 1.14, 95% CI 1.02-1.28). Patients who received anti-anaerobic antibiotics had decreased initial gut bacterial density (p=0.00038), increased microbiome expansion during hospitalisation (p=0.011) and domination by Enterobacteriaceae spp. (p=0.045). Enterobacteriaceae were also enriched among respiratory pathogens in anti-anaerobic-treated patients (p<2.2×10-16). In murine models, treatment with anti-anaerobic antibiotics increased susceptibility to Enterobacteriaceae pneumonia (p<0.05) and increased the lethality of hyperoxia (p=0.0002). CONCLUSIONS: In critically ill patients, early treatment with anti-anaerobic antibiotics is associated with increased mortality. Mechanisms may include enrichment of the gut with respiratory pathogens, but increased mortality is incompletely explained by infections alone. Given consistent clinical and experimental evidence of harm, the widespread use of anti-anaerobic antibiotics should be reconsidered.

Endovascular experience at an academic office-based procedure center.

OBJECTIVE: The number of office-based procedure centers with the capability of performing a wide range of endovascular procedures has substantially increased over the past decade. This shift in practice settings has occurred faster in the private sector as compared to the academic environment. The purpose of our study was to evaluate the clinical outcomes of endovascular procedures performed at a dedicated academic outpatient procedural center. METHODS: We reviewed the clinical data of 400 patients who underwent 499 endovascular procedures in a university-based, academic outpatient procedure center between November 2013 and December 2016. Outcomes analyzed included procedure-related complications, limb loss, mortality, and emergency department visits or hospital admissions that occurred within 30 days following the procedure. RESULTS: The 400 patients had a mean age of 65 ± 13 years with slightly more females (51%; n = 203) as compared to males (49%; n = 197). Most patients (71%; 284) were Caucasian while 80 (20%) were African-Americans. Associated comorbidities included hypertension (86%), diabetes mellitus (51%), chronic kidney disease (42%), and obesity (mean body mass index of 29 ± 6). Based on anesthetic risk, most were ASA class 3 (81%), while ASA 1 and 2 comprised 17% and ASA 4 only 2%. Medicare beneficiaries accounted for 254 (64%) of our patients. Pre-operative studies included mainly duplex ultrasound (62%) and other noninvasive arterial studies (57%).The mean procedural time was 58 min (range, 7 to 200) with an overall technical success rate of 97%. There were no deaths. Complications developed in 10 patients following the 483 procedures (2.1%) being hospitalized with four of them transferred directly to the emergency room. The reasons for these hospitalizations included acute limb ischemia, arterial pseudoaneurysm, deep vein thrombosis, congestive heart failure, myocardial infarction, and lower extremity pain not vascular in origin. Financial reimbursement at the office-based center was higher than that seen with hospital-based procedures. CONCLUSIONS: Endovascular procedures performed in an academic office-based procedure center are safe and associated with good clinical outcomes. A small minority of patients have subsequent ER visits or hospital admissions. Academic institutions should consider adding an office-based procedure center based on today's competitive healthcare market.

The Timing of Early Antibiotics and Hospital Mortality in Sepsis.

RATIONALE: Prior sepsis studies evaluating antibiotic timing have shown mixed results. OBJECTIVES: To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration. METHODS: Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors. MEASUREMENTS AND MAIN RESULTS: The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4-3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour's delay in antibiotic administration was 0.3% (95% CI, 0.01-0.6%; P = 0.04) for sepsis, 0.4% (95% CI, 0.1-0.8%; P = 0.02) for severe sepsis, and 1.8% (95% CI, 0.8-3.0%; P = 0.001) for shock. CONCLUSIONS: In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.

A systematic review of care management interventions targeting multimorbidity and high care utilization.

BACKGROUND: Evidence supporting the effectiveness of care management programs for complex patients has been inconclusive. However, past reviews have not focused on complexity primarily defined by multimorbidity and healthcare utilization. We conducted a systematic review of care management interventions targeting the following three patient groups: adults with two or more chronic medical conditions, adults with at least one chronic medical condition and concurrent depression, and adults identified based solely on high past or predicted healthcare utilization. METHODS: Eligible studies were identified from PubMed, published between 06/01/2005 and 05/31/2015, and reported findings from a randomized intervention that tested a comprehensive, care management intervention. Identified interventions were grouped based on the three "complex" categories of interest (described above). Two investigators extracted data using a structured abstraction form and assessed RCT quality. RESULTS: We screened 989 article titles for eligibility from which 847 were excluded. After reviewing the remaining 142 abstracts, 83 articles were excluded. We reviewed the full-text of 59 full-text articles and identified 15 unique RCTs for the final analysis. Of these 15 studies, two focused on patients with two or more chronic medical conditions, seven on patients with at least one chronic medical condition and depression, and six on patients with high past or predicted healthcare utilization. Measured outcomes included utilization, chronic disease measures, and patient-reported outcomes. The seven studies targeting patients with at least one chronic medical condition and depression demonstrated significant improvement in depression symptoms (ranging from 9.2 to 48.7% improvement). Of the six studies that focused on high utilizers, two showed small reductions in utilization. The quality of the research methodology in most of the studies (12/15) was rated fair or poor. CONCLUSIONS: Interventions were more likely to be successful when patients were selected based on having at least one chronic medical condition and concurrent depression, and when patient-reported outcomes were assessed. Future research should focus on the role of mental health in complex care management, finding better methods for identifying patients who would benefit most from care management, and determining which intervention components are needed for which patients.

CFTR regulatory region interacts with NBD1 predominantly via multiple transient helices.

The regulatory (R) region of the cystic fibrosis transmembrane conductance regulator (CFTR) is intrinsically disordered and must be phosphorylated at multiple sites for full CFTR channel activity, with no one specific phosphorylation site required. In addition, nucleotide binding and hydrolysis at the nucleotide-binding domains (NBDs) of CFTR are required for channel gating. We report NMR studies in the absence and presence of NBD1 that provide structural details for the isolated R region and its interaction with NBD1 at residue-level resolution. Several sites in the R region with measured fractional helical propensity mediate interactions with NBD1. Phosphorylation reduces the helicity of many R-region sites and reduces their NBD1 interactions. This evidence for a dynamic complex with NBD1 that transiently engages different sites of the R region suggests a structural explanation for the dependence of CFTR activity on multiple PKA phosphorylation sites.

Antibiotics cause metabolic changes in mice primarily through microbiome modulation rather than behavioral changes.

BACKGROUND: The microbiome is an important and increasingly-studied mediator of organismal metabolism, although how the microbiome affects metabolism remains incompletely understood. Many investigators use antibiotics to experimentally perturb the microbiome. However, antibiotics have poorly understood yet profound off-target effects on behavior and diet, including food and water aversion, that can confound experiments and limit their applicability. We thus sought to determine the relative influence of microbiome modulation and off-target antibiotic effects on the behavior and metabolic activity of mice. RESULTS: Mice treated with oral antibiotics via drinking water exhibited significant weight loss in fat, liver, and muscle tissue. These mice also exhibited a reduction in water and food consumption, with marked variability across antibiotic regimens. While administration of bitter-tasting but antimicrobially-inert compounds caused a similar reduction in water consumption, this did not cause tissue weight loss or reduced food consumption. Mice administered intraperitoneal antibiotics (bypassing the gastrointestinal tract) exhibited reduced tissue weights and oral intake, comparable to the effects of oral antibiotics. Antibiotic-treated germ-free mice did not have reduced tissue weights, providing further evidence that direct microbiome modulation (rather than behavioral effects) mediates these metabolic changes. CONCLUSIONS: While oral antibiotics cause profound effects on food and water consumption, antibiotic effects on organismal metabolism are primarily mediated by microbiome modulation. We demonstrate that tissue-specific weight loss following antibiotic administration is due primarily to microbiome effects rather than food and water aversion, and identify antibiotic regimens that effectively modulate gut microbiota while minimizing off-target behavioral effects.

Cerebral Hyperperfusion Syndrome Presenting As Status Epilepticus Following Carotid Endarterectomy.

Cerebral Hyperperfusion Syndrome (CHS) is a rare syndrome, commonly described as a prodrome of symptoms including a severe ipsilateral headache, focal neurological deficits, intracerebral hemorrhage, and occasionally includes seizures or encephalopathy. Our case involves a 76-year-old man who underwent a left carotid endarterectomy (CEA) for symptomatic high-grade stenosis of his left carotid artery. Post-operative day one, the patient was seen and examined in the early morning and found to be doing well, with blood pressures well-controlled and at his neurologic baseline. Three hours later, he was reported to have a sudden spike in his blood pressure and was experiencing focal motor seizures involving the right arm and face, both of which were unrelieved by anti-hypertensives and anti-seizure medications. The patient subsequently developed worsening respiratory function requiring intubation for status epilepticus. Repeat head and neck imaging with CT, CT angiography, and MRI demonstrated the known previous subacute infarct with new cerebral edema, patent carotid arteries bilaterally, and no acute infarct or intracerebral hemorrhage. While CHS is a rare syndrome with well-documented symptomatology, we present a unique case in which focal motor status epilepticus was the only presenting symptom in a patient who otherwise meets the criteria of CHS based on radiographic evidence of cerebral edema following an elective CEA.

Whole lung tissue is the preferred sampling method for amplicon-based characterization of murine lung microbiota.

BACKGROUND: Low-biomass microbiome studies (such as those of the lungs, placenta, and skin) are vulnerable to contamination and sequencing stochasticity, which obscure legitimate microbial signal. While human lung microbiome studies have rigorously identified sampling strategies that reliably capture microbial signal from these low-biomass microbial communities, the optimal sampling strategy for characterizing murine lung microbiota has not been empirically determined. Performing accurate, reliable characterization of murine lung microbiota and distinguishing true microbial signal from noise in these samples will be critical for further mechanistic microbiome studies in mice. RESULTS: Using an analytic approach grounded in microbial ecology, we compared bacterial DNA from the lungs of healthy adult mice collected via two common sampling approaches: homogenized whole lung tissue and bronchoalveolar lavage (BAL) fluid. We quantified bacterial DNA using droplet digital PCR, characterized bacterial communities using 16S rRNA gene sequencing, and systematically assessed the quantity and identity of bacterial DNA in both specimen types. We compared bacteria detected in lung specimens to each other and to potential source communities: negative (background) control specimens and paired oral samples. By all measures, whole lung tissue in mice contained greater bacterial signal and less evidence of contamination than did BAL fluid. Relative to BAL fluid, whole lung tissue exhibited a greater quantity of bacterial DNA, distinct community composition, decreased sample-to-sample variation, and greater biological plausibility when compared to potential source communities. In contrast, bacteria detected in BAL fluid were minimally different from those of procedural, reagent, and sequencing controls. CONCLUSIONS: An ecology-based analytical approach discriminates signal from noise in this low-biomass microbiome study and identifies whole lung tissue as the preferred specimen type for murine lung microbiome studies. Sequencing, analysis, and reporting of potential source communities, including negative control specimens and contiguous biological sites, are crucial for biological interpretation of low-biomass microbiome studies, independent of specimen type. Video abstract.

Association Between Peripheral Blood Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2) Ratio Time at Risk and Hospital Mortality in Mechanically Ventilated Patients.

INTRODUCTION: Acute respiratory failure requiring mechanical ventilation is a leading cause of mortality in the intensive care unit. Although single peripheral blood oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) ratios of hypoxemia have been evaluated to risk-stratify patients with acute respiratory distress syndrome, the utility of longitudinal SpO2/FiO2 ratios is unknown. OBJECTIVE: To assess time-based SpO2/FiO2 ratios ≤ 150-SpO2/FiO2 time at risk (SF-TAR)-for predicting mortality in mechanically ventilated patients. METHODS: Retrospective, observational cohort study of mechanically ventilated patients at 21 community and 2 academic hospitals. Association between the SF-TAR in the first 24 hours of ventilation and mortality was examined using multivariable logistic regression and compared with the worst recorded isolated partial pressure of arterial oxygen/fraction of inspired oxygen (P/F) ratio. RESULTS: In 28,758 derivation cohort admissions, every 10% increase in SF-TAR was associated with a 24% increase in adjusted odds of hospital mortality (adjusted odds ratio = 1.24; 95% confidence interval [CI] = 1.23-1.26); a similar association was observed in validation cohorts. Discrimination for mortality modestly improved with SF-TAR (area under the receiver operating characteristic curve [AUROC] = 0.81; 95% CI = 0.81-0.82) vs the worst P/F ratio (AUROC = 0.78; 95% CI = 0.78-0.79) and worst SpO2/FiO2 ratio (AUROC = 0.79; 95% CI = 0.79-0.80). The SF-TAR in the first 6 hours offered comparable discrimination for hospital mortality (AUROC = 0.80; 95% CI = 0.79-0.80) to the 24-hour SF-TAR. CONCLUSION: The SF-TAR can identify ventilated patients at increased risk of death, offering modest improvements compared with single SpO2/FiO2 and P/F ratios. This longitudinal, noninvasive, and broadly generalizable tool may have particular utility for early phenotyping and risk stratification using electronic health record data in ventilated patients.

Analysis of the Complete Genome of the Alkaliphilic and Phototrophic Firmicute Heliorestis convoluta Strain HHT.

Despite significant interest and past work to elucidate the phylogeny and photochemistry of species of the Heliobacteriaceae, genomic analyses of heliobacteria to date have been limited to just one published genome, that of the thermophilic species Heliobacterium (Hbt.) modesticaldum str. Ice1T. Here we present an analysis of the complete genome of a second heliobacterium, Heliorestis (Hrs.) convoluta str. HHT, an alkaliphilic, mesophilic, and morphologically distinct heliobacterium isolated from an Egyptian soda lake. The genome of Hrs. convoluta is a single circular chromosome of 3.22 Mb with a GC content of 43.1% and 3263 protein-encoding genes. In addition to culture-based observations and insights gleaned from the Hbt. modesticaldum genome, an analysis of enzyme-encoding genes from key metabolic pathways supports an obligately photoheterotrophic lifestyle for Hrs. convoluta. A complete set of genes encoding enzymes for propionate and butyrate catabolism and the absence of a gene encoding lactate dehydrogenase distinguishes the carbon metabolism of Hrs. convoluta from its close relatives. Comparative analyses of key proteins in Hrs. convoluta, including cytochrome c553 and the Fo alpha subunit of ATP synthase, with those of related species reveal variations in specific amino acid residues that likely contribute to the success of Hrs. convoluta in its highly alkaline environment.

Lung and gut microbiota are altered by hyperoxia and contribute to oxygen-induced lung injury in mice.

Inhaled oxygen, although commonly administered to patients with respiratory disease, causes severe lung injury in animals and is associated with poor clinical outcomes in humans. The relationship between hyperoxia, lung and gut microbiota, and lung injury is unknown. Here, we show that hyperoxia conferred a selective relative growth advantage on oxygen-tolerant respiratory microbial species (e.g., Staphylococcus aureus) as demonstrated by an observational study of critically ill patients receiving mechanical ventilation and experiments using neonatal and adult mouse models. During exposure of mice to hyperoxia, both lung and gut bacterial communities were altered, and these communities contributed to oxygen-induced lung injury. Disruption of lung and gut microbiota preceded lung injury, and variation in microbial communities correlated with variation in lung inflammation. Germ-free mice were protected from oxygen-induced lung injury, and systemic antibiotic treatment selectively modulated the severity of oxygen-induced lung injury in conventionally housed animals. These results suggest that inhaled oxygen may alter lung and gut microbial communities and that these communities could contribute to lung injury.

Chemoorganotrophic Bacteria From Lake Fryxell, Antarctica, Including Pseudomonas Strain LFY10, a Cold-Adapted, Halotolerant Bacterium Useful in Teaching Labs.

Lake Fryxell, situated in the McMurdo Dry Valleys of Antarctica, is an intriguing aquatic ecosystem because of its perennial ice cover, highly stratified water column, and extreme physicochemical conditions, which collectively restrict lake biodiversity to solely microbial forms. To expand our current understanding of the cultivable biodiversity of Lake Fryxell, water samples were collected from depths of 10 and 17 m, and pure cultures of eight diverse strains of aerobic, chemoorganotrophic bacteria were obtained. Despite having high 16S rRNA gene sequence similarity to mesophilic bacteria inhabiting various temperate environments, all Lake Fryxell isolates were psychrotolerant, with growth occurring at 0°C and optimal growth from 18-24°C for all isolates. Phylogenetic analyses showed the isolates to be members of six taxonomic groups, including the genera Brevundimonas, Arthrobacter, Sphingobium, Leifsonia, and Pseudomonas, as well as the family Microbacteriaceae (one strain could not reliably be assigned to a specific genus based on our analysis). Pseudomonas strain LFY10 stood out as a useful tool for teaching laboratory activities because of its substantial cold adaptation (visible growth is evident in 1-2 days at 4°C), beta-hemolytic activity, and halotolerance to 8.5% (w/v) NaCl. These cold-adapted bacteria likely play a role in carbon mineralization and other nutrient cycling in Lake Fryxell, and their characterization broadens our understanding of microbial biodiversity in aquatic polar ecosystems.

Calculation of residual dipolar couplings from disordered state ensembles using local alignment.

Residual dipolar couplings (RDCs) have been observed in disordered states of several proteins. While their nonuniform values were initially surprising, it has been shown that reasonable approximation of experimental RDCs can be obtained using simple statistical coil models and assuming global alignment of each structure, provided that many thousands of conformers are averaged. Here we show that, by using short local alignment tensors, we can achieve good agreement between experimental and simulated RDCs with far fewer structures than required when using global alignment. This makes the possibility of using RDCs as direct restraints in structural calculations of disordered proteins much more feasible. In addition, it provides insight into the nature of RDCs in disordered states, suggesting that they are primarily reporting on local structure.

Slow and steady wins the race: an examination of bacterial persistence.

Bacterial persistence is a state of metabolic dormancy among a small fraction (<1%) of a genetically identical population of cells that, as a result, becomes transiently resistant to environmental stressors. Such cells, called persisters, are able to survive indeterminate periods of exposure to challenging and even hostile environmental conditions, including nutrient deprivation, oxidative stress, or the presence of an antibiotic to which the bacterium would normally be susceptible. Subpopulations of cells having the persister phenotype is also a common feature of biofilms, in which limited space, hypoxia, and nutrient deficiencies all contribute to the onset of persistence. Microbiologists have been aware of bacterial persistence since the early days of antibiotic development. However, in recent years the significance of this phenomenon has been brought into new focus, as persistent bacterial infections that require multiple rounds of antibiotic treatment are becoming a more widespread clinical challenge. Here, we provide an overview of the major features of bacterial persistence, including the various conditions that precipitate persister formation and a discussion of several of the better-characterized molecular mechanisms that trigger this distinctive mode of bacterial dormancy.

Comparing Hospital Processes and Outcomes in California Medicare Beneficiaries: Simulation Prompts Reconsideration.

INTRODUCTION: This article is not a traditional research report. It describes how conducting a specific set of benchmarking analyses led us to broader reflections on hospital benchmarking. We reexamined an issue that has received far less attention from researchers than in the past: How variations in the hospital admission threshold might affect hospital rankings. Considering this threshold made us reconsider what benchmarking is and what future benchmarking studies might be like. Although we recognize that some of our assertions are speculative, they are based on our reading of the literature and previous and ongoing data analyses being conducted in our research unit. We describe the benchmarking analyses that led to these reflections. OBJECTIVES: The Centers for Medicare and Medicaid Services' Hospital Compare Web site includes data on fee-for-service Medicare beneficiaries but does not control for severity of illness, which requires physiologic data now available in most electronic medical records.To address this limitation, we compared hospital processes and outcomes among Kaiser Permanente Northern California's (KPNC) Medicare Advantage beneficiaries and non-KPNC California Medicare beneficiaries between 2009 and 2010. METHODS: We assigned a simulated severity of illness measure to each record and explored the effect of having the additional information on outcomes. RESULTS: We found that if the admission severity of illness in non-KPNC hospitals increased, KPNC hospitals' mortality performance would appear worse; conversely, if admission severity at non-KPNC hospitals' decreased, KPNC hospitals' performance would appear better. CONCLUSION: Future hospital benchmarking should consider the impact of variation in admission thresholds.