Vitamin D Deficiency and Long-Term Cognitive Impairment Among Older Adult Emergency Department Patients

Introduction: Approximately 16% of acutely ill older adults develop new, long-term cognitive impairment (LTCI), many of whom initially seek care in the emergency department (ED). Currently, no effective interventions exist to prevent LTCI after an acute illness. Identifying early and modifiable risk factors for LTCI is the first step toward effective therapy. We hypothesized that Vitamin D deficiency at ED presentation was associated with LTCI in older adults.Methods: This was an observational analysis of a prospective cohort study that enrolled ED patients ≥ 65 years old who were admitted to the hospital for an acute illness. All patients were enrolled within four hours of ED presentation. Serum Vitamin D was measured at enrollment and Vitamin D deficiency was defined as serum concentrations <20 mg/dL. We measured pre-illness and six-month cognition using the short form Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), which ranges from 1 to 5 (severe cognitive impairment). Multiple linear regression was performed to determine whether Vitamin D deficiency was associated with poorer six-month cognition adjusted for pre-illness IQCODE and other confounders. We incorporated a two-factor interaction into the regression model to determine whether the relationship between Vitamin D deficiency and six-month cognition was modified by pre-illness cognition.Results: We included a total of 134 older ED patients; the median (interquartile range [IQR]) age was 74 (69, 81) years old, 61 (46%) were female, and 14 (10%) were nonwhite race. The median (IQR) vitamin D level at enrollment was 25 (18, 33) milligrams per deciliter and 41 (31%) of enrolled patients met criteria for vitamin D deficiency. Seventy-seven patients survived and had a six-month IQCODE. In patients with intact pre-illness cognition (IQCODE of 3.13), Vitamin D deficiency was significantly associated with worsening six-month cognition (β-coefficient: 0.43, 95% CI, 0.07 to 0.78, p = 0.02) after adjusting for pre-illness IQCODE and other confounders. Among patients with pre-illness dementia (IQCODE of 4.31), no association with Vitamin D deficiency was observed (β-coefficient: -0.1;, 95% CI, [-0.50-0.27], p = 0.56).Conclusion: Vitamin D deficiency was associated with poorer six-month cognition in acutely ill older adult ED patients who were cognitively intact at baseline. Future studies should determine whether early Vitamin D repletion in the ED improves cognitive outcomes in acutely ill older patients.

Validation of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits

<p>Abstract</p> <p>Background</p> <p>Accurate identification of hypoglycemia cases by <it>International Classification of Diseases, Ninth Revision, Clinical Modification </it>(ICD-9-CM) codes will help to describe epidemiology, monitor trends, and propose interventions for this important complication in patients with diabetes. Prior hypoglycemia studies utilized incomplete search strategies and may be methodologically flawed. We sought to validate a new ICD-9-CM coding algorithm for accurate identification of hypoglycemia visits.</p> <p>Methods</p> <p>This was a multicenter, retrospective cohort study using a structured medical record review at three academic emergency departments from July 1, 2005 to June 30, 2006. We prospectively derived a coding algorithm to identify hypoglycemia visits using ICD-9-CM codes (250.3, 250.8, 251.0, 251.1, 251.2, 270.3, 775.0, 775.6, and 962.3). We confirmed hypoglycemia cases by chart review identified by candidate ICD-9-CM codes during the study period. The case definition for hypoglycemia was documented blood glucose 3.9 mmol/l or emergency physician charted diagnosis of hypoglycemia. We evaluated individual components and calculated the positive predictive value.</p> <p>Results</p> <p>We reviewed 636 charts identified by the candidate ICD-9-CM codes and confirmed 436 (64%) cases of hypoglycemia by chart review. Diabetes with other specified manifestations (250.8), often excluded in prior hypoglycemia analyses, identified 83% of hypoglycemia visits, and unspecified hypoglycemia (251.2) identified 13% of hypoglycemia visits. The absence of any predetermined co-diagnosis codes improved the positive predictive value of code 250.8 from 62% to 92%, while excluding only 10 (2%) true hypoglycemia visits. Although prior analyses included only the first-listed ICD-9 code, more than one-quarter of identified hypoglycemia visits were outside this primary diagnosis field. Overall, the proposed algorithm had 89% positive predictive value (95% confidence interval, 86–92) for detecting hypoglycemia visits.</p> <p>Conclusion</p> <p>The proposed algorithm improves on prior strategies to identify hypoglycemia visits in administrative data sets and will enhance the ability to study the epidemiology and design interventions for this important complication of diabetes care.</p

Emerging Roles for MicroRNAs in Perioperative Medicine

MicroRNAs (miRNAs) are small, non-protein-coding, single-stranded RNAs. They function as posttranscriptional regulators of gene expression by interacting with target mRNAs. This process prevents translation of target mRNAs into a functional protein. miRNAs are considered to be functionally involved in virtually all physiologic processes, including differentiation and proliferation, metabolism, hemostasis, apoptosis, and inflammation. Many of these functions have important implications for anesthesiology and critical care medicine. Studies indicate that miRNA expression levels can be used to predict the risk for eminent organ injury or sepsis. Pharmacologic approaches targeting miRNAs for the treatment of human diseases are currently being tested in clinical trials. The present review highlights the important biological functions of miRNAs and their usefulness as perioperative biomarkers and discusses the pharmacologic approaches that modulate miRNA functions for disease treatment. In addition, the authors discuss the pharmacologic interactions of miRNAs with currently used anesthetics and their potential to impact anesthetic toxicity and side effects

Variable Access to Immediate Bedside Ultrasound in the Emergency Department

Objective: Use of bedside emergency department (ED) ultrasound has become increasingly important for the clinical practice of emergency medicine (EM). We sought to evaluate differences in the availability of immediate bedside ultrasound based on basic ED characteristics and physician staffing.Methods: We surveyed ED directors in all 351 EDs in Colorado, Georgia, Massachusetts, and Oregon between January and April 2009. We assessed access to bedside ED ultrasound by the question: “Is bedside ultrasound available immediately in the ED?” ED characteristics included location, visit volume, admission rate, percent uninsured, total emergency physician full-time equivalents and proportion of EM board-certified (BC) or EM board-eligible (BE) physicians. Data analysis used chi-square tests and multivariable logistical regression to compare differences in access to bedside ED ultrasound by ED characteristics and staffing.Results: We received complete responses from 298 (85%) EDs. Immediate access to bedside ultrasound was available in 175 (59%) EDs. ED characteristics associated with access to bedside ultrasound were: location (39% for rural vs. 71% for urban, P20%] rates, P<0.001); and EM BC/BE physicians (26% for EDs with a low percentage [0-20%] vs.74% for EDs with a high percentage [≥80%], P<0.001).Conclusion: U.S. EDs differ significantly in their access to immediate bedside ultrasound. Smaller, rural EDs and those staffed by fewer EM BC/BE physicians more frequently lacked access to immediate bedside ultrasound in the ED. [West J Emerg Med. 2011;12(1):96-99.

Improved care of acute exacerbation of chronic obstructive pulmonary disease in two academic emergency departments

Background: Although several chronic obstructive pulmonary disease (COPD) practice guidelines have been published, there is sparse data on the actual emergency department (ED) management of acute exacerbation of COPD (AECOPD). Aims: Our objectives were to examine concordance of ED care of AECOPD in older patients with guideline recommendations and to evaluate whether concordance has improved over time in two academic EDs. Methods: Data were obtained from two cohort studies on AECOPD performed in two academic EDs during two different time periods, 2000 and 2005–2006. Both studies included ED patients, aged 55 and older, who presented with AECOPD, and cases were confirmed by emergency physicians. Data on ED management and disposition were obtained from chart review for both cohorts. Results: The analysis included 272 patients: 72 in the 2000 database and 200 in the 2005–2006 database. The mean age of the patients was 72 years; 50% were women and 80% white. In 2005–2006, overall concordance with guideline recommendations was high (for chest radiography, pulse oximetry, bronchodilators, all ≥ 90%), except for arterial blood gas testing (7% among the admitted) and discharge medication with systemic corticosteroids (42%). Compared to the 2000 data, the use of systemic corticosteroids in the ED improved from 53 to 77% [absolute improvement: 24%, 95% confidence interval (CI): 11–37%], and the use of antibiotics among the patients with respiratory infection symptoms improved from 56 to 78% (absolute improvement: 22%, 95% CI: 6–38%). Conclusions: Overall concordance with guideline-recommended care for AECOPD was high in two academic EDs, and some emergency treatments have improved over time

The sensitivity of qSOFA calculated at triage and during emergency department treatment to rapidly identify sepsis patients.

The quick sequential organ failure assessment (qSOFA) score has been proposed as a means to rapidly identify adult patients with suspected infection, in pre-hospital, Emergency Department (ED), or general hospital ward locations, who are in a high-risk category with increased likelihood of poor outcomes: a greater than 10% chance of dying or an increased likelihood of spending 3 or more days in the ICU. This score is intended to replace the use of systemic inflammatory response syndrome (SIRS) criteria as a screening tool; however, its role in ED screening and identification has yet to be fully elucidated. In this retrospective observational study, we explored the performance of triage qSOFA (tqSOFA), maximum qSOFA, and first initial serum lactate (\u3e 3 mmol/L) at predicting in-hospital mortality and compared these results to those for the initial SIRS criteria obtained in triage. A total of 2859 sepsis cases were included and the in-hospital mortality rate was 14.4%. The sensitivity of tqSOFA ≥ 2 and maximum qSOFA ≥ 2 to predict in-hospital mortality were 33% and 69%, respectively. For comparison, the triage SIRS criteria and the initial lactate \u3e 3 mmol/L had sensitivities of 82% and 65%, respectively. These results demonstrate that in a large ED sepsis database the earliest measurement of end organ impairment, tqSOFA, performed poorly at identifying patients at increased risk of mortality and maximum qSOFA did not significantly outperform initial serum lactate levels

Consistent Effects of Early Remdesivir on Symptoms and Disease Progression Across At-Risk Outpatient Subgroups: Treatment Effect Heterogeneity in PINETREE Study

INTRODUCTION: In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% by day 28 in high-risk, non-hospitalized patients. Here we report results of assessment of heterogeneity of treatment effect (HTE) of early outpatient remdesivir, focusing on time from symptom onset and number of baseline risk factors (RFs). METHODS: PINETREE was a double-blind, placebo-controlled trial of non-hospitalized patients with COVID-19 who were randomized within 7 days of symptom onset and had ≥ 1 RF for disease progression (age ≥ 60 years, obesity [body mass index ≥ 30], or certain coexisting medical conditions). Patients received remdesivir intravenously (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. RESULTS: In this subgroup analysis, HTE of remdesivir by time from symptom onset at treatment initiation and number of baseline RFs was not detected. Treatment with remdesivir reduced COVID-19-related hospitalizations independent of stratification by time from symptom onset to randomization. Of patients enrolled ≤ 5 days from symptom onset, 1/201 (0.5%) receiving remdesivir and 9/194 (4.6%) receiving placebo were hospitalized (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.82). Of those enrolled at > 5 days from symptom onset, 1/78 (1.3%) receiving remdesivir and 6/89 (6.7%) receiving placebo were hospitalized (HR 0.19; 95% CI 0.02-1.61). Remdesivir was also effective in reducing COVID-19-related hospitalizations when stratified by number of baseline RFs for severe disease. Of patients with ≤ 2 RFs, 0/159 (0.0%) receiving remdesivir and 4/164 (2.4%) receiving placebo were hospitalized; of those with ≥ 3 RFs, 2/120 (1.7%) receiving remdesivir and 11/119 (9.2%) receiving placebo were hospitalized (HR 0.16; 95% CI 0.04-0.73). CONCLUSIONS: In the outpatient setting, benefit of remdesivir initiated within 7 days of symptoms appeared to be consistent across patients with RFs. Therefore, it may be reasonable to broadly treat patients with remdesivir regardless of comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov number NCT04501952

Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients

BACKGROUND: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level,[50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality