Age-Stratified 30-day Rehospitalization and Mortality and Predictors of Rehospitalization Among Patients With Systemic Lupus Erythematosus: A Medicare Cohort Study.

OBJECTIVE: Recent studies suggest young adults with systemic lupus erythematosus (SLE) have high 30-day readmission rates, which may necessitate tailored readmission reduction strategies. To aid in risk stratification for future strategies, we measured 30-day rehospitalization and mortality rates among Medicare beneficiaries with SLE and determined rehospitalization predictors by age. METHODS: In a 2014 20% national Medicare sample of hospitalizations, rehospitalization risk and mortality within 30 days of discharge were calculated for young (aged 18-35 yrs), middle-aged (aged 36-64 yrs), and older (aged 65+ yrs) beneficiaries with and without SLE. Multivariable generalized estimating equation models were used to predict rehospitalization rates among patients with SLE by age group using patient, hospital, and geographic factors. RESULTS: Among 1.39 million Medicare hospitalizations, 10,868 involved beneficiaries with SLE. Hospitalized young adult beneficiaries with SLE were more racially diverse, were living in more disadvantaged areas, and had more comorbidities than older beneficiaries with SLE and those without SLE. Thirty-day rehospitalization was 36% among young adult beneficiaries with SLE-40% higher than peers without SLE and 85% higher than older beneficiaries with SLE. Longer length of stay and higher comorbidity risk score increased odds of rehospitalization in all age groups, whereas specific comorbid condition predictors and their effect varied. Our models, which incorporated neighborhood-level socioeconomic disadvantage, had moderate-to-good predictive value (C statistics 0.67-0.77), outperforming administrative data models lacking comprehensive social determinants in other conditions. CONCLUSION: Young adults with SLE on Medicare had very high 30-day rehospitalization at 36%. Considering socioeconomic disadvantage and comorbidities provided good prediction of rehospitalization risk, particularly in young adults. Young beneficiaries with SLE with comorbidities should be a focus of programs aimed at reducing rehospitalizations.

The increasing impact of length of stay "outliers" on length of stay at an urban academic hospital.

BACKGROUND: As healthcare systems strive for efficiency, hospital "length of stay outliers" have the potential to significantly impact a hospital's overall utilization. There is a tendency to exclude such "outlier" stays in local quality improvement and data reporting due to their assumed rare occurrence and disproportionate ability to skew mean and other summary data. This study sought to assess the influence of length of stay (LOS) outliers on inpatient length of stay and hospital capacity over a 5-year period at a large urban academic medical center. METHODS: From January 2014 through December 2019, 169,645 consecutive inpatient cases were analyzed and assigned an expected LOS based on national academic center benchmarks. Cases in the top 1% of national sample LOS by diagnosis were flagged as length of stay outliers. RESULTS: From 2014 to 2019, mean outlier LOS increased (40.98 to 45.11 days), as did inpatient LOS with outliers excluded (5.63 to 6.19 days). Outlier cases increased both in number (from 297 to 412) and as a percent of total discharges (0.98 to 1.56%), and outlier patient days increased from 6.7 to 9.8% of total inpatient plus observation days over the study period. CONCLUSIONS: Outlier cases utilize a disproportionate and increasing share of hospital resources and available beds. The current tendency to exclude such outlier stays in data reporting due to assumed rare occurrence may need to be revisited. Outlier stays require distinct and targeted interventions to appropriately reduce length of stay to both improve patient care and maintain hospital capacity.

Antihypertensive medication initiation among young adults with regular primary care use.

BACKGROUND: Young adults with hypertension have the lowest prevalence of controlled blood pressure compared to middle-aged and older adults. Uncontrolled hypertension, even among young adults, increases future cardiovascular event risk. However, antihypertensive medication initiation is poorly understood among young adults and may be an important intervention point for this group. OBJECTIVE: The purpose of this study was to compare rates and predictors of antihypertensive medication initiation between young adults and middle-aged and older adults with incident hypertension and regular primary care contact. DESIGN: A retrospective analysis PARTICIPANTS: Adults ≥ 18 years old (n = 10,022) with incident hypertension and no prior antihypertensive prescription, who received primary care at a large, Midwestern, academic practice from 2008-2011. MAIN MEASURES: The primary outcome was time from date of meeting hypertension criteria to antihypertensive medication initiation, or blood pressure normalization without medication. Kaplan-Meier analysis was used to estimate the probability of antihypertensive medication initiation over time. Cox proportional-hazard models (HR; 95% CI) were fit to identify predictors of delays in medication initiation, with a subsequent subpopulation analysis for young adults (18-39 years old). KEY RESULTS: After a mean follow-up of 20 (±13) months, 34% of 18-39 year-olds with hypertension met the endpoint, compared to 44% of 40-59 year-olds and 56% of ≥ 60 year-olds. Adjusting for patient and provider factors, 18-39 year-olds had a 44% slower rate of medication initiation (HR 0.56; 0.47-0.67) than ≥ 60 year-olds. Among young adults, males, patients with mild hypertension, and White patients had a slower rate of medication initiation. Young adults with Medicaid and more clinic visits had faster rates. CONCLUSIONS: Even with regular primary care contact and continued elevated blood pressure, young adults had slower rates of antihypertensive medication initiation than middle-aged and older adults. Interventions are needed to address multifactorial barriers contributing to poor hypertension control among young adults.

Disparities in 30-day readmission rates among Medicare enrollees with dementia.

BACKGROUND: Readmissions contribute to excessive care costs and burden for people living with dementia. Assessments of racial disparities in readmissions among dementia populations are lacking, and the role of social and geographic risk factors such as individual-level exposure to greater neighborhood disadvantage is poorly understood. We examined the association between race and 30-day readmissions in a nationally representative sample of Black and non-Hispanic White individuals with dementia diagnoses. METHODS: This retrospective cohort study used 100% Medicare fee-for-service claims from all 2014 hospitalizations nationwide among Medicare enrollees with dementia diagnosis linked to patient, stay, and hospital factors. The sample consisted of 1,523,142 hospital stays among 945,481 beneficiaries. The relationship between all cause 30-day readmissions and the explanatory variable of self-reported race (Black, non-Hispanic White) was examined via generalized estimating equations approach adjusting for patient, stay, and hospital-level characteristics to model 30-day readmission odds. RESULTS: Black Medicare beneficiaries had 37% higher readmission odds compared to White beneficiaries (unadjusted OR 1.37, CI 1.35-1.39). This heightened readmission risk persisted after adjusting for geographic factors (OR 1.33, CI 1.31-1.34), social factors (OR 1.25, CI 1.23-1.27), hospital characteristics (OR 1.24, CI 1.23-1.26), stay-level factors (OR 1.22, CI 1.21-1.24), demographics (OR 1.21, CI 1.19-1.23), and comorbidities (OR 1.16, CI 1.14-1.17), suggesting racially-patterned disparities in care account for a portion of observed differences. Associations varied by individual-level exposure to neighborhood disadvantage such that the protective effect of living in a less disadvantaged neighborhood was associated with reduced readmissions for White but not Black beneficiaries. Conversely, among White beneficiaries, exposure to the most disadvantaged neighborhoods associated with greater readmission rates compared to White beneficiaries residing in less disadvantaged contexts. CONCLUSIONS: There are significant racial and geographic disparities in 30-day readmission rates among Medicare beneficiaries with dementia diagnoses. Findings suggest distinct mechanisms underlying observed disparities differentially influence various subpopulations.

NFAT and IRF proteins regulate transcription of the anti-HIV gene, APOBEC3G.

The human cytidine deaminase APOBEC3G (A3G) is an innate restriction factor that inhibits human immunodeficiency virus, type 1 (HIV-1) replication. Regulation of A3G gene expression plays an important role in this suppression. Currently, an understanding of the mechanism of this gene regulation is largely unknown. Here, we have identified and characterized a TATA-less core promoter with an NFAT/IRF-4 composite binding site that confers cell type-specific transcriptional regulation. We found that A3G expression is critically dependent on NFATc1/NFATc2 and IRF-4. When either NFATc1 or NFATc2 and IRF-4 were co-expressed, A3G promoter activity was observed in cells that normally lack A3G expression and expression was not detected in the presence of the individual factors. This induced A3G expression allowed normally permissive CEMss cells to adopt a nonpermissive state, able to resist an HIV-1Δvif challenge. This represents the first reporting of manipulating the restrictive state of a cell type via gene regulation. Identification of NFAT and IRF family members as critical regulators of A3G expression offers important insight into the transcriptional control mechanisms that regulate innate immune responses and identifies specific targets for therapeutic intervention aimed at effectively boosting our natural immunity, in the form of a host defensive factor, against HIV-1.

Race, Sex, and Neighborhood Socioeconomic Disparities in Ablation of Ventricular Tachycardia Within a National Medicare Cohort.

Background Ventricular tachycardia (VT) ablation significantly improves our ability to control VT, yet little is known about whether disparities exist in delivery of this technology. Methods and Results Using a national 100% Medicare inpatient data set of beneficiaries admitted with VT from January 1, 2014, through November 30, 2014, multivariable logistic regression techniques were used to examine the sociodemographic and clinical characteristics associated with receiving ablation. Census block group-level neighborhood socioeconomic disadvantage was measured for each patient by the Area Deprivation Index, a composite measure of socioeconomic disadvantage consisting of education, income, housing, and employment factors. Among 131 645 patients admitted with VT, 2190 (1.66%) received ablation. After adjustment for comorbidities, hospital characteristics, and sociodemographics, female sex (odds ratio [OR], 0.75 [95% CI, 0.67-0.84]), identifying as Black race (OR, 0.75 [95% CI, 0.62-0.90] compared with identifying as White race), and living in a highly socioeconomically disadvantaged neighborhood (national Area Deprivation Index percentile of >85%) (OR, 0.81 [95% CI, 0.69-0.95] versus Area Deprivation Index ≤85%) were associated with significantly lower odds of receiving ablation. Conclusions Female patients, patients identifying as Black race, and patients living in the most disadvantaged neighborhoods are 19% to 25% less likely to receive ablation during hospitalization with VT. The cause of and solutions for these disparities require further investigation.

The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif.

The human protein apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like-3G (APOBEC3G), also known as CEM-15, mediates a newly described form of innate resistance to retroviral infection by catalyzing the deamination of deoxycytidine to deoxyuridine in viral cDNA replication intermediates. Because DNA deamination takes place after virus entry into target cells, APOBEC3G function is dependent on its association with the viral nucleoprotein complexes that synthesize cDNA and must therefore be incorporated into virions as they assemble in infected cells. Here we show that the HIV-1 virion infectivity factor (Vif) protein protects the virus from APOBEC3G-mediated inactivation by preventing its incorporation into progeny virions, thus allowing the ensuing infection to proceed without DNA deamination. In addition to helping exclude APOBEC3G from nascent virions, Vif also removes APOBEC3G from virus-producing cells by inducing its ubiquitination and subsequent degradation by the proteasome. Our findings indicate that pharmacologic strategies aimed at stabilizing APOBEC3G in HIV-1 infected cells should be explored as potential HIV/AIDS therapeutics.

Health Policy Advocacy Engagement: A Physician Survey.

PURPOSE: Physicians can play an important role in shaping health policy. The purpose of this study was to determine characteristics of physicians participating in health policy and barriers and facilitators to their advocacy. METHODS: A modified previously validated survey instrument was mailed to physicians affiliated with the University of Wisconsin on October 12, 2018. Three follow-up emails were sent, and the response period closed January 30, 2019. Twenty-eight items were included in the survey tool. Respondents were considered highly engaged if they: (a) reported involvement in predetermined high impact areas, (b) had self-reported weekly or monthly advocacy involvement, or (c) had more than 10% dedicated work time for advocacy. RESULTS: Eight hundred eighty-six of 1,432 physicians responded (61.9%), of which 133 (15.0%) were highly engaged. Highly engaged respondents were more commonly male (57.1%), White (90.2%), of nonsurgical specialties (80.5%), and Democrat (55.6%) or Independent (27.1%). Those not highly engaged were more likely to report "I don't know how to get involved." Less than half of all respondents received any advocacy education, with professional organizations providing the majority of education through conferences and distribution of materials. Only 2.5% of respondents had more than 10% of work time dedicated to health policy. CONCLUSIONS: Engagement in health policy exists on a spectrum, but only a small percent of physicians are highly engaged, and very few have dedicated work time for advocacy. Certain demographics predominate the advocacy voice, and health policy training opportunities are lacking.

The Hospital Readmissions Reduction Program and Observation Hospitalizations.

The Centers for Medicare & Medicaid Services (CMS) Hospital Readmissions Reduction Program (HRRP) penalizes hospitals having excess inpatient rehospitalizations within 30 days of index inpatient stays for targeted conditions. Observation hospitalizations are increasing in frequency and may clinically resemble inpatient hospitalizations, yet HRRP excludes observation in index and 30-day rehospitalization counts. Using 100% 2014 Medicare fee-for-service claims and CMS's 30-day rehospitalization methodology, we modeled how observation hospitalizations impact HRRP metrics when counted as index (denominator) and 30-day (numerator) rehospitalizations. Of 3,806,772 index hospitalizations for HRRP conditions, 418,923 (11%) were observation; 18% (155,553/876,033) of rehospitalizations were invisible to HRRP due to observation hospitalization as index (34%; 63,740/188,430), 30-day outcome (53%; 100,343/188,430), or both (13%; 24,347/188,430). By ignoring observation hospitalizations as index and 30-day events, nearly one of five HRRP rehospitalizations is missed. Policymakers might consider this an opportunity to address broad challenges of the two-tiered observation and inpatient hospital billing distinction.

Antibiotic utilization variability among training services at an academic medical center: An observational study.

OBJECTIVE: Evaluate the difference in antibiotic prescribing between various levels of resident training or attending types. DESIGN: Observational, retrospective study. SETTING: Tertiary-care, academic medical center in Madison, Wisconsin. METHODS: We measured antibiotic utilization from January 1, 2016, through December 31, 2018, in our general medicine (GM) and hospitalist services. The GM1 service is staffed by outpatient internal medicine physicians, the GM2 service is staffed by geriatricians and hospitalists, and the GM3 service is staffed by only hospitalists. The GMA service is led by junior resident physicians, and the GMB service is led by senior resident physicians. We measured utilization using days of therapy (DOT) per 1,000 patient days (PD). In a secondary analysis based on antibiotic spectrum, we used average DOT per 1,000 PD. RESULTS: Teaching services prescribed more antibiotics than nonteaching services (671.6 vs 575.2 DOT per 1,000 PD; P < .0001). Junior resident-led services used more antibiotics than senior resident-led services (740.9 vs 510.0 DOT per 1,000 PD; P < .0001). Overall, antibiotic prescribing was numerically similar between various attending physician backgrounds. A secondary analysis showed that GM services prescribed more broad-spectrum, anti-MRSA, and anti-pseudomonal antibiotics than the hospitalist services. GM junior resident-led services prescribed more broad-spectrum, anti-MRSA, and antipseudomonal therapy compared to their senior counterparts. CONCLUSIONS: Antibiotics were prescribed at a significantly higher rate in services associated with trainees than those without. Services led by a junior resident physician prescribed antibiotics at a significantly higher rate than services led by a senior resident. Interventions to reduce unnecessary antibiotic exposure should be targeted toward resident physicians, especially junior trainees.

One Quarter of Medicare Hospitalizations in Patients with Systemic Lupus Erythematosus Readmitted within Thirty Days.

OBJECTIVE: Thirty-day hospital readmissions in systemic lupus erythematosus (SLE) approach proportions in Medicare-reported conditions including heart failure (HF). We compared adjusted 30-day readmission and mortality among SLE, HF, and general Medicare to assess predictors informing readmission prevention. METHODS: This database study used a 20% sample of all US Medicare 2014 adult hospitalizations to compare risk of 30-day readmission and mortality among admissions with SLE, HF, and neither per discharge diagnoses (if both SLE and HF, classified as SLE). Inclusion required live discharge and ≥12 months of Medicare A/B before admission to assess baseline covariates including patient, geographic, and hospital factors. Analysis used observed and predicted probabilities, and multivariable GEE models clustered by patient to report adjusted risk ratios (ARRs) of 30-day readmission and mortality. RESULTS: SLE admissions (n=10,868) were younger, predominantly female, more likely to be Black, disabled, and have Medicaid or end-stage renal disease (ESRD). Observed 30-day readmissions of 24% were identical for SLE and HF (p = 0.6), and higher than other Medicare (16%, p < 0.001). Both SLE and HF had elevated readmission risk (ARR 1.08, (95% CI (1.04, 1.13)); 1.11, (1.09, 1.13)). SLE readmissions were higher for Black (30%) versus White (21%) populations, and highest in ages 18-33 (39%) and ESRD (37%). Admissions of Black patients with SLE from least disadvantaged neighborhoods had highest 30-day mortality (9% versus 3% White). CONCLUSION: Thirty-day SLE readmissions rivaled HF at 24%. Readmission prevention programs should engage young, ESRD patients with SLE and examine potential causal gaps in SLE care and transitions.

Critical illness-induced dysglycaemia: diabetes and beyond.

Type 2 diabetes has reached epidemic proportions in many parts of the world. The disease is projected to continue to increase and double within the foreseeable future. Dysglycaemia develops in the form of hyperglycaemia, hypoglycaemia and marked glucose variability in critically ill adults whether they are known to have premorbid diabetes or not. Patients with such glucose dysregulation have increased morbidity and mortality. Whether this is secondary to cause and effect from dysglycaemia or is just related to critical illness remains under intense investigation. Identification of intensive care unit (ICU) patients with unrecognised diabetes remains a challenge. Further, there are few data regarding the development of type 2 diabetes in survivors after hospital discharge. This commentary introduces the concept of critical illness-induced dysglycaemia as an umbrella term that includes the spectrum of abnormal glucose homeostasis in the ICU. We outline the need for further studies in the area of glucose regulation and for follow-up of the natural history of abnormal glucose control during ICU admission and beyond.

What Is an Observation Stay? Evaluating the Use of Hospital Observation Stays in Medicare.

BACKGROUND/OBJECTIVES: Observation stays are increasingly common for older adults, yet little is known about the extent to which they are being used as the Centers for Medicare and Medicaid Services (CMS) originally intended for unscheduled or acute problems and whether different types of services are reflected in current billing practices. DESIGN: Observational cohort study. SETTING/PARTICIPANTS: A total of 867,165 qualifying observation stays identified from 451,408 patients using Medicare fee-for-service claims data from a nationally representative 20% beneficiary sample between January 1, 2014, and November 30, 2014. MEASUREMENTS: Using descriptive and multivariable logistic model analytic approaches, we evaluated the patient, stay, and hospital characteristics associated with the most common billing practice for observation stays (charge revenue center 0761 exclusively) vs all other practices. RESULTS: Sixty-three percent of observation stays were billed exclusively under the 0761 revenue center and were more likely to be for preplanned chronic conditions consisting of short-term treatments (eg, chemotherapy, radiation therapy, wound care, paracentesis, epidural spinal injection). These stays appeared to be used for recurrent single-day visits, given their strong association with prior visits and a high rate of reobservation (41.4%), with frequent return stays appearing in a 7-day pattern. CONCLUSION: Nearly two-thirds of observation stays are billed using only the 0761 revenue code and appear to be for prescheduled, repeated treatments-differing substantially from CMS' explicitly stated purpose as a form of care used while a healthcare provider determines whether a patient presenting for unscheduled or acute conditions requires inpatient hospital admission or can be safely discharged. Guidance is needed from CMS to clarify the appropriate role of observation stays, with discussion as to whether episodic single-day, planned treatment for chronic conditions not originating in the emergency department should be billed as observation stays or placed under another mechanism. Subsequent research is needed to understand how the current use of observation stays impact patient out-of-pocket costs. J Am Geriatr Soc 68:1568-1572, 2020.

Improving Healthcare Value: COVID-19 Emergency Regulatory Relief and Implications for Post-Acute Skilled Nursing Facility Care.

Rarely, if ever, does a national healthcare system experience such rapid and marked change as that seen with the COVID-19 pandemic. In March 2020, the president of the United States declared a national health emergency, enabling the Department of Health & Human Services authority to grant temporary regulatory waivers to facilitate efficient care delivery in a variety of healthcare settings. The statutory requirement that Medicare beneficiaries stay three consecutive inpatient midnights to qualify for post-acute skilled nursing facility coverage is one such waiver. This so-called Three Midnight Rule, dating back to the 1960s as part of the Social Security Act, is being scrutinized more than half a century later given the rise in observation hospital stays. Despite the tragic emergency circumstances prompting waivers, the Centers for Medicare & Medicaid Services and Congress now have a unique opportunity to evaluate potential improvements revealed by COVID-19 regulatory relief and should consider permanent reform of the Three Midnight Rule.

Thirty-Day Re-observation, Chronic Re-observation, and Neighborhood Disadvantage.

OBJECTIVE: To determine whether neighborhood socioeconomic disadvantage, as determined by the Area Deprivation Index, increases 30-day hospital re-observation risk. PARTICIPANTS AND METHODS: This retrospective study of 20% Medicare fee-for-service beneficiary observation stays from January 1, 2014, to November 30, 2014, included 319,980 stays among 273,308 beneficiaries. We evaluated risk for a 30-day re-observation following an index observation stay for those living in the 15% most disadvantaged compared with the 85% least disadvantaged neighborhoods. RESULTS: Overall, 4.5% (270,600 of 6,080,664) of beneficiaries had index observation stays, which varied by disadvantage (4.3% [232,568 of 5,398,311] in the least disadvantaged 85% compared with 5.6% [38,032 of 682,353] in the most disadvantaged 15%). Patients in the most disadvantaged neighborhoods had a higher 30-day re-observation rate (2857 of 41,975; 6.8%) compared with least disadvantaged neighborhoods (13,543 of 278,005; 4.9%); a 43% increased risk (unadjusted odds ratio [OR], 1.43; 95% CI, 1.31 to 1.55). After adjustment, this risk remained (adjusted OR, 1.13; 95% CI, 1.04 to 1.22). Discharge to a skilled nursing facility reduced 30-day re-observation risk (OR, 0.63; 95% CI, 0.57 to 0.69), whereas index observation length of stay of 4 or more days (3 midnights) conferred increased risk (OR, 1.29; 95% CI, 1.09 to 1.52); those living in disadvantaged neighborhoods were less likely to discharge to skilled nursing facilities and more likely to have long index stays. Beneficiaries with more than one 30-day re-observation (chronic re-observation) had progressively greater disadvantage by number of stays (adjusted incident rate ratio, 1.08; 95% CI, 1.02 to 1.14). Observation prevalence varied nationally. CONCLUSION: Thirty-day re-observation, especially chronic re-observation, is highly associated with socioeconomic neighborhood disadvantage, even after accounting for factors such as race, disability, and Medicaid eligibility. Beneficiaries least able to pay are potentially most vulnerable to costs from serial re-observations and challenges of Medicare observation policy, which may discourage patients from seeking necessary care.

Glucose control in the intensive care unit.

OBJECTIVE: Hyperglycemia, be it secondary to diabetes, impaired glucose tolerance, impaired fasting glucose, or stress-induced is common in the critically ill. Hyperglycemia and glucose variability in intensive care unit (ICU) patients has some experts calling for routine administration of intensive insulin therapy to normalize glucose levels in hyperglycemic patients. Others, however, have raised concerns over the optimal glucose level, the accuracy of measurements, the resources required to attain tight glycemic control (TGC), and the impact of TGC across the heterogeneous ICU population in patients with diabetes, previously undiagnosed diabetes or stress-induced hyperglycemia. Increased variability in glucose levels during critical illness and the therapeutic intervention thereof have recently been reported to have a deleterious impact on survival, particularly in nondiabetic hyperglycemic patients. The incidence of hypoglycemia (<40 mg/dL or 2.2 mmol) associated with TGC is reported to be as high as 18.7%, by Van den Berghe in a medical ICU, although application of various approaches and computer-based algorithms may improve this. The impact of hypoglycemia, particularly in patients with septic shock and those with neurologic compromise, warrants further evaluation. This review briefly discusses the epidemiology of hyperglycemia in the acutely ill and glucose metabolism in the critically ill. It comments on present limitations in glucose monitoring, outlines current glucose management approaches in the critically ill, and the transition from the ICU to the intermediate care unit or ward. It closes with comment on future developments in glycemic care of the critically ill. METHODS: The awareness of the potential deleterious impact of hyperglycemia was heightened after Van den Berghe et al presented their prospective trial in 2001. Therefore, source data were obtained from PubMed and Cochrane Analysis searches of the medical literature, with emphasis on the time period after 2000. Recent meta-analyses were reviewed, expert editorial opinion collated, and the Web site of the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation Trial investigated. SUMMARY AND CONCLUSIONS: Hyperglycemia develops commonly in the critically ill and impacts outcome in patients with diabetes but, even more so, in patients with stress-induced hyperglycemia. Despite calls for TGC by various experts and regulatory agencies, supporting data remain somewhat incomplete and conflicting. A recently completed large international study, Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation, should provide information to further guide best practice. This concise review interprets the current state of adult glycemic management guidelines to provide a template for care as new information becomes available.

Identifying Observation Stays In Medicare Data: Policy Implications of a Definition.

Observation stays are increasingly common, yet no standard method to identify observation stays in Medicare claims is available, including events with status change. To determine the claims patterns of Medicare observation stays, define comprehensive claims-based methodology for future Medicare observation research and data reporting, and identify policy implications of such definition, we identified potential observation events in a 2014 20% random sample of Medicare beneficiaries with both Part A and B claims and at least 1 acute care stay (1,667,660 events). Observation revenue center (ORC) and Healthcare Common Procedure Coding System codes occurring within 30 days of an inpatient hospitalization were recorded. A total of 125,920 (7.6%) events had an ORC code, and 75,502 (4.5%) were in the outpatient revenue center. Claims patterns varied tremendously, and almost half (47.3%, 59,529) of the ORC codes were associated with an inpatient claim, indicating status change and demonstrating a need for clarity in observation policy. The proposed University of Wisconsin method identified 72,858 of 75,502 (96.5%) events with ORC codes as observation stays, and provides a comprehensive, reproducible methodology.

Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity.

The antiretroviral activity of the cellular enzyme APOBEC3G has been attributed to the excessive deamination of cytidine (C) to uridine (U) in minus strand reverse transcripts, a process resulting in guanosine (G) to adenosine (A) hypermutation of plus strand DNAs. The HIV-1 Vif protein counteracts APOBEC3G by inducing proteasomal degradation and exclusion from virions through recruitment of a cullin5 ECS E3 ubiquitin ligase complex. APOBEC3G belongs to the APOBEC protein family, members of which possess consensus (H/C)-(A/V)-E-(X)24-30-P-C-(X)2-C cytidine deaminase motifs. Earlier analyses of APOBEC-1 have defined specific residues that are important for zinc coordination, proton transfer, and, therefore, catalysis within this motif. Because APOBEC3G contains two such motifs, we used site-directed mutagenesis of conserved residues to assess each region's contribution to anti-HIV-1 activity. Surprisingly, whereas either the N- or C-terminal domain could confer antiviral function in tissue culture-based infectivity assays, only an intact C-terminal motif was essential for DNA mutator activity. These findings reveal the nonequivalency of APOBEC3G's N- and C-terminal domains and imply that APOBEC3G-mediated DNA editing may not always be necessary for antiviral activity. Accordingly, we propose that APOBEC3G can achieve an anti-HIV-1 effect through an undescribed mechanism that is distinct from cytidine deamination.