Exploring Delirium's Heterogeneity: Association Between Arousal Subtypes at Initial Presentation and 6-Month Mortality in Older Emergency Department Patients.

OBJECTIVES: To determine how delirium subtyped by level of arousal at initial presentation affects 6-month mortality. DESIGN: This was a preplanned secondary analysis of two prospective cohort studies. SETTING: Academic tertiary care emergency department (ED). PARTICIPANTS: 1,084 ED patients who were 65 years old or older. MEASUREMENTS: At the time of enrollment, trained research personnel performed the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation Sedation Score to determine delirium and level of arousal, respectively. Patients were categorized as having no delirium, delirium with normal arousal, delirium with decreased arousal, or delirium with increased arousal. Death was ascertained by medical record review and the Social Security Death Index. Cox proportional hazard regression was used to analyze the association between delirium arousal subtypes and 6-month mortality. RESULTS: Delirium with normal arousal was the only subtype that was significantly associated with increased 6-month mortality (hazard ratio [HR]: 3.1, 95% confidence interval [CI]: 1.3-7.4) compared with the no delirium group after adjusting for confounders. The HRs for delirium with decreased and increased arousal were 1.4 (95% CI: 0.9-2.1) and 1.3 (95% CI: 0.3-5.4), respectively. CONCLUSIONS: Delirious ED patients with normal arousal at initial presentation had a threefold increased hazard of death within 6 months compared with patients without delirium. There was a trend towards increased hazard of death in delirious ED patients with decreased arousal, but this relationship did not reach statistical significance. These data suggest that subtyping delirium by arousal may have prognostic value but requires confirmation with a larger study.

Chronic Pain and Associated Factors in India and Nepal: A Pilot Study of the Vanderbilt Global Pain Survey.

BACKGROUND: Evaluation and treatment of chronic pain worldwide are limited by the lack of standardized assessment tools incorporating consistent definitions of pain chronicity and specific queries of known social and psychological risk factors for chronic pain. The Vanderbilt Global Pain Survey (VGPS) was developed as a tool to address these concerns, specifically in the low- and middle-income countries where global burden is highest. METHODS: The VGPS was developed using standardized and cross-culturally validated metrics, including the Brief Pain Inventory and World Health Organization Disability Assessment Scale, as well as the Pain Catastrophizing Scale, the Fibromyalgia Survey Questionnaire along with queries about pain attitudes to assess the prevalence of chronic pain and disability along with its psychosocial and emotional associations. The VGPS was piloted in both Nepal and India over a 1-month period in 2014, allowing for evaluation of this tool in 2 distinctly diverse cultures. RESULTS: Prevalence of chronic pain in Nepal and India was consistent with published data. The Nepali cohort displayed a pain point prevalence of 48%-50% along with some form of disability present in approximately one third of the past 30 days. Additionally, 11% of Nepalis recorded pain in 2 somatic sites and 39% of those surveyed documented a history of a traumatic event. In the Indian cohort, pain point prevalence was approximately 24% to 41% based on the question phrasing, and any form of disability was present in 6 of the last 30 days. Of the Indians surveyed, 11% reported pain in 2 somatic sites, with only 4% reporting a previous traumatic event. Overall, Nepal had significantly higher chronic pain prevalence, symptom severity, widespread pain, and self-reported previous traumatic events, yet lower reported pain severity. CONCLUSIONS: Our findings confirm prevalent chronic pain, while revealing pertinent cultural differences and survey limitations that will inform future assessment strategies. Specific areas for improvement identified in this VGPS pilot study included survey translation methodology, redundancy of embedded metrics and cultural limitations in representative sampling and in detecting the prevalence of mental health illness, catastrophizing behavior, and previous traumatic events. International expert consensus is needed.

Risk factors for delirium after cardiac surgery: a historical cohort study outlining the influence of cardiopulmonary bypass.

PURPOSE: Cardiopulmonary bypass (CPB) induces a significant inflammatory response that may increase the risk for delirium. We hypothesized that exposure to CPB during coronary artery bypass grafting (CABG) surgery would correlate with an increased risk of delirium. METHODS: We reviewed clinical data from two databases at our medical centre - the Cardiac Surgery Perioperative Outcomes Database and the Society of Thoracic Surgeons Database. Patients undergoing elective CABG surgery (on-pump and off-pump) from November 1, 2009 to September 30, 2015 were included in the study. Delirium was defined as any postoperative positive Confusion Assessment Method for the Intensive Care Unit exam during the intensive care unit stay. We performed logistic regression to isolate the association between CPB exposure and delirium adjusted for predetermined risk factors and potential confounders. RESULTS: During the study period, 2,280 patients underwent elective CABG surgery, with 384 patients (16.9%) exposed to CPB. Delirium was diagnosed in 451 patients (19.8%). Exposure to CPB showed a significant independent association with delirium. Patients exposed to CPB for 142 min (90th percentile of CPB duration) vs those exposed for 54 min (10th percentile) had an adjusted relative risk (RR) of delirium of 2.18 (95% confidence interval [CI], 1.39 to 3.07; P = 0.002) vs a RR of 1.51 (95% CI, 0.92 to 2.29; P = 0.10), respectively. CONCLUSIONS: The use and duration of cardiopulmonary bypass were associated with an increased risk of delirium in patients undergoing CABG surgery. TRIAL REGISTRATION: www.clinicaltrials.gov , NCT02548975. Registered 4 September 2015.

Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes.

BACKGROUND: Type 2 diabetes patients often initiate treatment with a sulfonylurea and subsequently intensify their therapy with insulin. However, information on optimal treatment regimens for these patients is limited. OBJECTIVE: To compare risk of cardiovascular disease (CVD) and hypoglycemia between sulfonylurea initiators who switch to or add insulin. DESIGN: This was a retrospective cohort assembled using national Veterans Health Administration (VHA), Medicare, and National Death Index databases. PARTICIPANTS: Veterans who initiated diabetes treatment with a sulfonylurea between 2001 and 2008 and intensified their regimen with insulin were followed through 2011. MAIN MEASURES: The association between insulin versus sulfonylurea + insulin and time to CVD or hypoglycemia were evaluated using Cox proportional hazard models in a 1:1 propensity score-matched cohort. CVD included hospitalization for acute myocardial infarction or stroke, or cardiovascular mortality. Hypoglycemia included hospitalizations or emergency visits for hypoglycemia, or outpatient blood glucose measurements <60 mg/dL. Subgroups included age < 65 and ≥ 65 years and estimated glomerular filtration rate ≥ 60 and < 60 ml/min. KEY FINDINGS: There were 1646 and 3728 sulfonylurea monotherapy initiators who switched to insulin monotherapy or added insulin, respectively. The 1596 propensity score-matched patients in each group had similar baseline characteristics at insulin initiation. The rate of CVD per 1000 person-years among insulin versus sulfonylurea + insulin users were 49.3 and 56.0, respectively [hazard ratio (HR) 0.85, 95 % confidence interval (CI) 0.64, 1.12]. Rates of first and recurrent hypoglycemia events per 1000 person-years were 74.0 and 100.0 among insulin users compared to 78.9 and 116.8 among sulfonylurea plus insulin users, yielding HR (95 % CI) of 0.94 (0.76, 1.16) and 0.87 (0.69, 1.10), respectively. Subgroup analysis results were consistent with the main findings. CONCLUSIONS: Compared to sulfonylurea users who added insulin, those who switched to insulin alone had numerically lower CVD and hypoglycemia events, but these differences in risk were not statistically significant.

Risk of hypoglycemia following intensification of metformin treatment with insulin versus sulfonylurea.

BACKGROUND: Hypoglycemia remains a common life-threatening event associated with diabetes treatment. We compared the risk of first or recurrent hypoglycemia event among metformin initiators who intensified treatment with insulin versus sulfonylurea. METHODS: We assembled a retrospective cohort using databases of the Veterans Health Administration, Medicare and the National Death Index. Metformin initiators who intensified treatment with insulin or sulfonylurea were followed to either their first or recurrent hypoglycemia event using Cox proportional hazard models. Hypoglycemia was defined as hospital admission or an emergency department visit for hypoglycemia, or an outpatient blood glucose value of less than 3.3 mmol/L. We conducted additional analyses for risk of first hypoglycemia event, with death as the competing risk. RESULTS: Among 178,341 metformin initiators, 2948 added insulin and 39,990 added sulfonylurea. Propensity score matching yielded 2436 patients taking metformin plus insulin and 12,180 taking metformin plus sulfonylurea. Patients took metformin for a median of 14 (interquartile range [IQR] 5-30) months, and the median glycated hemoglobin level was 8.1% (IQR 7.2%-9.9%) at intensification. In the group who added insulin, 121 first hypoglycemia events occurred, and 466 first events occurred in the group who added sulfonylurea (30.9 v. 24.6 events per 1000 person-years; adjusted hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.06-1.59). For recurrent hypoglycemia, there were 159 events in the insulin group and 585 events in the sulfonylurea group (39.1 v. 30.0 per 1000 person-years; adjusted HR 1.39, 95% CI 1.12-1.72). In separate competing risk analyses, the adjusted HR for hypoglycemia was 1.28 (95% CI 1.04-1.56). INTERPRETATION: Among patients using metformin who could use either insulin or sulfonylurea, the addition of insulin was associated with a higher risk of hypoglycemia than the addition of sulfonylurea. This finding should be considered by patients and clinicians when discussing the risks and benefits of adding insulin versus a sulfonylurea.

Diabetes treatment intensification and associated changes in HbA1c and body mass index: a cohort study.

BACKGROUND: To describe common type 2 diabetes treatment intensification regimens, patients' characteristics and changes in glycated hemoglobin (HbA1c) and body mass index (BMI). METHODS: We constructed a national retrospective cohort of veterans initially treated for diabetes with either metformin or sulfonylurea from 2001 through 2008, using Veterans Health Administration (VHA) and Medicare data. Patients were followed through September, 2011 to identify common diabetes treatment intensification regimens. We evaluated changes in HbA1c and BMI post-intensification for metformin-based regimens. RESULTS: We identified 323,857 veterans who initiated diabetes treatment. Of these, 55 % initiated metformin, 43 % sulfonylurea and 2 % other regimens. Fifty percent (N = 89,057) of metformin initiators remained on metformin monotherapy over a median follow-up 58 months (interquartile range [IQR] 35, 74). Among 80,725 patients who intensified metformin monotherapy, the four most common regimens were addition of sulfonylurea (79 %), thiazolidinedione [TZD] (6 %), or insulin (8 %), and switch to insulin monotherapy (2 %). Across these regimens, median HbA1c values declined from a range of 7.0-7.8 % (53-62 mmol/mol) at intensification to 6.6-7.0 % (49-53 mmol/mol) at 1 year, and remained stable up to 3 years afterwards. Median BMI ranged between 30.5 and 32 kg/m(2) at intensification and increased very modestly in those who intensified with oral regimens, but 1-2 kg/m(2) over 3 years among those who intensified with insulin-based regimens. CONCLUSIONS: By 1 year post-intensification of metformin monotherapy, HbA1c declined in all four common intensification regimens, and remained close to 7 % in subsequent follow-up. BMI increased substantially for those on insulin-based regimens.

Development and Patient Satisfaction of a New Telemedicine Service for Pain Management at Massachusetts General Hospital to the Island of Martha's Vineyard.

OBJECTIVE: Patients in remote areas lack access to specialist care and pain management services. In order to provide pain management care to patients remote from our center, we created a telemedicine pain clinic (telepain) at Massachusetts General Hospital (MGH) in Boston, MA to extend services to the Island of Martha's Vineyard. DESIGN: Over 13 months, 238 telepain video clinic evaluations were conducted. A pain physician visited the island 1-2 days per month and performed 121 interventions. Given the novelty of telemedicine clinics, we surveyed patients to gauge satisfaction and identify perceived weaknesses in our approach that could be addressed. Forty-nine consecutive patients answered a 14-question, 5-point balanced Likert-scale survey with 1 (no, definitely not) being most negative and 5 (yes, definitely) being most positive. SETTING: Patients on Martha's Vineyard referred for pain management consultation services via telemedicine. PATIENTS: Forty-nine consecutive patients evaluated via telemedicine. INTERVENTIONS: Likert-scale survey administered. MEASURES: Questions measured patient impressions of video-based visits with their doctor, convenience of the visit, concerns about privacy, and whether they would recommend such a visit, among other items. RESULTS: Mean respondent scores for each question were >4.3 indicating a favorable impression of the telepain clinic experience. Lowest mean scores were found when respondents were asked to compare the care they received by telepain versus an in-person visit, or whether they were able to develop a friendly relationship with the doctor. CONCLUSIONS: The results suggest an overall positive reception of telepain by patients, yet highlight the challenge of building a patient-physician relationship remotely.

Association between intensification of metformin treatment with insulin vs sulfonylureas and cardiovascular events and all-cause mortality among patients with diabetes.

IMPORTANCE: Preferred second-line medication for diabetes treatment after metformin failure remains uncertain. OBJECTIVE: To compare time to acute myocardial infarction (AMI), stroke, or death in a cohort of metformin initiators who added insulin or a sulfonylurea. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort constructed with national Veterans Health Administration, Medicare, and National Death Index databases. The study population comprised veterans initially treated with metformin from 2001 through 2008 who subsequently added either insulin or sulfonylurea. Propensity score matching on characteristics was performed, matching each participant who added insulin to 5 who added a sulfonylurea. Patients were followed through September 2011 for primary analyses or September 2009 for cause-of-death analyses. MAIN OUTCOMES AND MEASURES: Risk of a composite outcome of AMI, stroke hospitalization, or all-cause death was compared between therapies with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, cholesterol level, hemoglobin A1c level, creatinine level, blood pressure, body mass index, and comorbidities. RESULTS: Among 178,341 metformin monotherapy patients, 2948 added insulin and 39,990 added a sulfonylurea. Propensity score matching yielded 2436 metformin + insulin and 12,180 metformin + sulfonylurea patients. At intensification, patients had received metformin for a median of 14 months (IQR, 5-30), and hemoglobin A1c level was 8.1% (IQR, 7.2%-9.9%). Median follow-up after intensification was 14 months (IQR, 6-29 months). There were 172 vs 634 events for the primary outcome among patients who added insulin vs sulfonylureas, respectively (42.7 vs 32.8 events per 1000 person-years; adjusted hazard ratio [aHR], 1.30; 95% CI, 1.07-1.58; P = .009). Acute myocardial infarction and stroke rates were statistically similar, 41 vs 229 events (10.2 and 11.9 events per 1000 person-years; aHR, 0.88; 95% CI, 0.59-1.30; P = .52), whereas all-cause death rates were 137 vs 444 events, respectively (33.7 and 22.7 events per 1000 person-years; aHR, 1.44; 95% CI, 1.15-1.79; P = .001). There were 54 vs 258 secondary outcomes: AMI, stroke hospitalizations, or cardiovascular deaths (22.8 vs 22.5 events per 1000 person-years; aHR, 0.98; 95% CI, 0.71-1.34; P = .87). CONCLUSIONS AND RELEVANCE: Among patients with diabetes who were receiving metformin, the addition of insulin vs a sulfonylurea was associated with an increased risk of a composite of nonfatal cardiovascular outcomes and all-cause mortality. These findings require further investigation to understand risks associated with insulin use in these patients.

Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control.

BACKGROUND AND OBJECTIVE: We recently reported that kidney function declined faster among initiators of sulfonylureas compared to metformin; however, sulfonylurea use compared to metformin use was also associated with increases in body mass index (BMI) and systolic blood pressure (SBP). We sought to determine if differences between sulfonylureas and metformin on kidney function decline were mediated by differential effects on BMI, SBP, or glucose control. METHODS: We identified 13,238 veterans who initiated sulfonylurea or metformin treatment (2000­2007) with a baseline estimated glomerular filtration rate (eGFR) >60 mL/minute, and followed them until a study event occurred, non-persistence on treatment, loss of follow-up, or end of the study. The composite outcome was a sustained decline from baseline eGFR of ≥25%, end-stage renal disease, or death. We estimated the association of cumulative measurements of potential mediators including BMI, SBP, and glycated hemoglobin on the study outcome. We determined if controlling for these time-varying covariates accounted for the differences in outcome between sulfonylurea and metformin initiators. RESULTS: Compared to sulfonylurea use, metformin use was associated with a lower risk for renal function decline or death [adjusted hazard ratio (aHR) 0.82, 95% confidence interval 0.70, 0.97]. This protective association remained significant [aHR 0.83 (0.70­0.98)] when accounting for the cumulative time-varying measurements of the three mediators of interest. CONCLUSION: Metformin initiation was associated with a lower risk of kidney function decline or death compared to sulfonylureas, which which appeared to be independent of changes in BMI, SBP, and glycated hemoglobin over time.

Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study.

BACKGROUND: The effects of sulfonylureas and metformin on outcomes of cardiovascular disease (CVD) in type 2 diabetes are not well-characterized. OBJECTIVE: To compare the effects of sulfonylureas and metformin on CVD outcomes (acute myocardial infarction and stroke) or death. DESIGN: Retrospective cohort study. SETTING: National Veterans Health Administration databases linked to Medicare files. PATIENTS: Veterans who initiated metformin or sulfonylurea therapy for diabetes. Patients with chronic kidney disease or serious medical illness were excluded. MEASUREMENTS: Composite outcome of hospitalization for acute myocardial infarction or stroke, or death, adjusted for baseline demographic characteristics; medications; cholesterol, hemoglobin A1c, and serum creatinine levels; blood pressure; body mass index; health care utilization; and comorbid conditions. RESULTS: Among 253 690 patients initiating treatment (98 665 with sulfonylurea therapy and 155 025 with metformin therapy), crude rates of the composite outcome were 18.2 per 1000 person-years in sulfonylurea users and 10.4 per 1000 person-years in metformin users (adjusted incidence rate difference, 2.2 [95% CI, 1.4 to 3.0] more CVD events with sulfonylureas per 1000 person-years; adjusted hazard ratio [aHR], 1.21 [CI, 1.13 to 1.30]). Results were consistent for both glyburide (aHR, 1.26 [CI, 1.16 to 1.37]) and glipizide (aHR, 1.15 [CI, 1.06 to 1.26]) in subgroups by CVD history, age, body mass index, and albuminuria; in a propensity score-matched cohort analysis; and in sensitivity analyses. LIMITATION: Most of the veterans in the study population were white men; data on women and minority groups were limited but reflective of the Veterans Health Administration population. CONCLUSION: Use of sulfonylureas compared with metformin for initial treatment of diabetes was associated with an increased hazard of CVD events or death. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and the U.S. Department of Health and Human Services.

Comparative effectiveness of incident oral antidiabetic drugs on kidney function.

Diabetes is a major cause of chronic kidney disease, and oral antidiabetic drugs are the mainstay of therapy for most patients with Type 2 diabetes. Here we evaluated their role on renal outcomes by using a national Veterans Administration database to assemble a retrospective cohort of 93,577 diabetic patients who filled an incident oral antidiabetic drug prescription for metformin, sulfonylurea, or rosiglitazone, and had an estimated glomerular filtration rate (eGFR) of 60 ml/min or better. The primary composite outcome was a persistent decline in eGFR from baseline of 25% or more (eGFR event) or a diagnosis of end-stage renal disease (ESRD). The secondary outcome was an eGFR event, ESRD, or death. Sensitivity analyses included using a more stringent definition of the eGFR event requiring an eGFR <60 ml/min per 1.73 m(2) in addition to the 25% or more decline; controlling for baseline proteinuria thereby restricting data to 15,065 patients; and not requiring persistent treatment with the initial oral antidiabetic drug. Compared to patients using metformin, sulfonylurea users had an increased risk for both the primary and the secondary outcome, each with an adjusted hazard ratio of 1.20. Results of sensitivity analyses were consistent with the main findings. The risk associated with rosiglitazone was similar to metformin for both outcomes. Thus, compared to metformin, oral antidiabetic drug treatment with sulfonylureas increased the risk of a decline in eGFR, ESRD, or death.

Initiation of sulfonylureas versus metformin is associated with higher blood pressure at one year.

PURPOSE: To determine if incident oral antidiabetic drug (OAD) use was associated with 12-month systolic blood pressure (BP) and if this was mediated through body mass index (BMI) changes. METHODS: A retrospective cohort of veterans with hypertension who initiated metformin (n = 2057) or sulfonylurea (n = 1494) between 1 January 2000 and 31 December 2007 in the Veterans Administration Mid-South Network was assembled. Patients were included if they had complete covariates, including 12-month BP and BMI, and persisted on therapy for 12 months. Linear regression was conducted to investigate the effect of OADs on 12-month systolic BP adjusting for demographics, glycated hemoglobin, creatinine, BMI, health care utilization, and comorbidities, including cardiovascular disease (CVD). A second analysis examined if these effects were mediated by BMI change. The secondary outcome was the proportion of patients who had a controlled BP (≤ 140/90 mmHg) at 12 months adjusted for baseline BP and covariates. RESULTS: Patients were white (82%) males (97%) with median age of 64 years (interquartile range [IQR] 57, 72), and 27% had history of CVD. Sulfonylurea users had a 1.33 mmHg (0.16, 2.50, p = 0.03) higher 12-month systolic BP than metformin users. The median change in BMI from OAD initiation to 12 months was -0.76 (IQR -1.78, 0.07) and 0.21 (IQR -0.57, 1.03) among metformin and sulfonylurea users, respectively. In a model adjusting for BMI change, the difference in 12-month systolic BP between sulfonylurea and metformin users became insignificant (0.23 (-1.00, 1.45), p = 0.72), while one BMI unit change was associated with an increase in 12-month systolic BP of 1.07 mmHg (0.74, 1.40, p < 0.0001). At 12 months, 68.3% of metformin patients had controlled BP versus 64.2% of sulfonylurea patients (p = 0.01). CONCLUSIONS: Compared with metformin, sulfonylurea initiation was associated with increased systolic BP at 12 months, which appears to be mediated by the differential effects of these drugs on BMI.

Reweighted Mahalanobis distance matching for cluster-randomized trials with missing data.

PURPOSE: This paper introduces an improved tool for designing matched-pairs randomized trials. The tool allows the incorporation of clinical and other knowledge regarding the relative importance of variables used in matching and allows for multiple types of missing data. The method is illustrated in the context of a cluster-randomized trial. A Web application and an R package are introduced to implement the method and incorporate recent advances in the area. METHODS: Reweighted Mahalanobis distance (RMD) matching incorporates user-specified weights and imputed values for missing data. Weight may be assigned to missingness indicators to match on missingness patterns. Three examples are presented, using real data from a cohort of 90 Veterans Health Administration sites that had at least 100 incident metformin users in 2007. Matching is utilized to balance seven factors aggregated at the site level. Covariate balance is assessed for 10,000 randomizations under each strategy: simple randomization, matched randomization using the Mahalanobis distance, and matched randomization using the RMD. RESULTS: The RMD matching achieved better balance than simple randomization or MD randomization. In the first example, simple and MD randomization resulted in a 10% chance of seeing an absolute mean difference of greater than 26% in the percent of nonwhite patients per site; the RMD dramatically reduced that to 6%. The RMD achieved significant improvement over simple randomization even with as much as 20% of the data missing. CONCLUSIONS: Reweighted Mahalanobis distance matching provides an easy-to-use tool that incorporates user knowledge and missing data.

Effect of Cistanche deserticola on Rumen Microbiota and Rumen Function in Grazing Sheep.

For a long time, veterinary drugs and chemical additives have been widely used in livestock and poultry breeding to improve production performance. However, problems such as drug residues in food are causing serious concerns. The use of functional plants and their extracts to improve production performance is becoming increasingly popular. This study aimed to evaluate the effect of Cistanche deserticola in sheep feed on rumen flora and to analyze the causes to provide a theoretical basis for the future use of Cistanche deserticola as a functional substance to improve sheep production performance. A completely randomized experimental design was adopted using 24 six-month-old sheep males divided into four groups (six animals in each group) which were fed a basic diet composed of alfalfa and tall fescue grass. The C. deserticola feed was provided to sheep at different levels (0, 2, 4, and 6%) as experimental treatments. On the last day (Day 75), ruminal fluid was collected through a rumen tube for evaluating changes in rumen flora. The test results showed that Prevotella_1, Lactobacillus, and Rikenellaceae_RC9_gut_group were the dominant species at the genus level in all samples. Lactobacillus, Rikenellaceae_RC9_gut_group, Ruminococcaceae_NK4A214_group, Butyrivibrio_2, and Christensenellaceae_R-7_group differed significantly in relative abundance among the treatment groups. The polysaccharides in C. deserticola was the major factor influencing the alteration in rumen flora abundance, and had the functions of improving rumen fermentation environment and regulating rumen flora structure, etc. Hence, C. deserticola can be used to regulate rumen fermentation in grazing sheep to improve production efficiency.

The effect of incident antidiabetic regimens on lipid profiles in veterans with type 2 diabetes: a retrospective cohort.

OBJECTIVE: Effects of oral antidiabetic drugs (OADs) on lipids may influence cardiovascular outcomes. Our aim was to compare time to initiation of lipid lowering medication (LLM) and 12-month lipid profiles among new OAD users. METHODS: We identified a retrospective cohort of 17,774 veterans who received care at Veterans Administration (VA) Mid-South Network with a first OAD from 1 January 2000 to 31 December 2007. There were 6917 patients (38.9%) not on a LLM at baseline, and 3871 (56%) had complete covariates. Incident users of sulfonylurea and combination metformin + sulfonylurea were compared to metformin users for time to LLM initiation. Incident users of these OADs and thiazolidendiones were included in comparison of 12-month low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TGs), and total cholesterol. All analyses adjusted for demographics, lipids, HbA1C, healthcare utilization, and cardiovascular disease at baseline. RESULTS: The median time to starting LLM was 2.35 years (interquartile range 0.96, 4.6) following metformin initiation and not statistically different for users of sulfonylureas, or combination OADs. Compared to metformin users, 12-month HDL was 1.35 mg/dl (95%CI: -2.01, -0.72) lower and TGs were 5.7% higher (95%CI: 1.5%, 10.0%) for sulfonylurea users; TGs were 24.8% (95%CI: 0.7%, 54.5%) higher for thiazolidinedione users. Statin users had LDL and total cholesterol 16.7 mg/dl (95%CI: -19.9, -13.5) and 18.6 mg/dl (95%CI: -22.1, -15.1) lower than non-statin users, respectively. CONCLUSIONS: Time to LLM initiation was similar between OADs. Metformin use resulted in more favorable lipids at 12 months compared to sulfonylureas or thiazolidinediones.

Measuring and comparing safety climate in intensive care units.

BACKGROUND: Learning about the factors that influence safety climate and improving the methods for assessing relative performance among hospital or units would improve decision-making for clinical improvement. OBJECTIVES: To measure safety climate in intensive care units (ICU) owned by a large for-profit integrated health delivery systems; identify specific provider, ICU, and hospital factors that influence safety climate; and improve the reporting of safety climate data for comparison and benchmarking. RESEARCH DESIGN: We administered the Safety Attitudes Questionnaire (SAQ) to clinicians, staff, and administrators in 110 ICUs from 61 hospitals. SUBJECTS: A total of 1502 surveys (43% response) from physicians, nurses, respiratory therapists, pharmacists, mangers, and other ancillary providers. MEASURES: The survey measured safety climate across 6 domains: teamwork climate; safety climate; perceptions of management; job satisfaction; working conditions; and stress recognition. Percentage of positive scores, mean scores, unadjusted random effects, and covariate-adjusted random effect were used to rank ICU performance. RESULTS: The cohort was characterized by a positive safety climate. Respondents scored perceptions of management and working conditions significantly lower than the other domains of safety climate. Respondent job type was significantly associated with safety climate and domain scores. There was modest agreement between ranking methodologies using raw scores and random effects. CONCLUSIONS: The relative proportion of job type must be considered before comparing safety climate results across organizational units. Ranking methodologies based on raw scores and random effects are viable for feedback reports. The use of covariate-adjusted random effects is recommended for hospital decision-making.

Glycemic and weight changes after persistent use of incident oral diabetes therapy: a Veterans Administration retrospective cohort study.

PURPOSE: Systematic reviews have reported that sulfonylureas and metformin were as effective in reducing hemoglobin A1c (A1C) as other oral antidiabetic drugs (OADs) in clinical trial populations. Data on comparative effectiveness of OADs in other populations is limited. The objective was to compare the effectiveness of incident OAD regimens in reducing A1C and to compare the effect of OADs on body mass index (BMI). METHODS: Retrospective cohort study using data from the Veterans Affairs Mid-South network (2001-2007). Of 18 205 veterans who filled 19 511 incident OAD prescriptions, 2096 had complete covariates, persisted on their incident treatment for 12 months, and had baseline and 12-month A1C values. For the BMI analysis, 2484 patients had complete information. Incident OAD regimens included metformin and sulfonylureas. Primary outcomes were 12-month A1C and BMI, which were compared controlling for demographic characteristics, baseline A1C and BMI, psychiatric diagnoses, and healthcare utilization. RESULTS: Median [interquartile range (IQR)] A1C decreased from 7.1% [6.5, 7.8] at baseline to 6.5% [6.0, 7.0] at 12 months. Twelve month-A1C in sulfonylurea users was similar to metformin users. The median [IQR] BMI decreased from 31.1 [27.8, 34.9] to 30.7 [27.5, 34.5] kg/m(2). Sulfonylureas were associated with a significantly higher 12-month BMI than metformin (12-month adjusted mean difference: 1.05 kg/m(2), 95%CI: 0.90-1.20, p < 0.0001). CONCLUSIONS: These analyses support the use of metformin as first choice of OAD because of similar glycemic control but improved BMI when compared to sulfonylureas.

Cistanche deserticola Addition Improves Growth, Digestibility, and Metabolism of Sheep Fed on Fresh Forage from Alfalfa/Tall Fescue Pasture.

This study is targeted at evaluating whether C. deserticola addition promotes digestion, nitrogen and energy use, and methane production of sheep fed on fresh forage from alfalfa/tall fescue pastures. The sheep feeding trial was conducted with four addition levels with C. deserticola powder, and a basal diet of fresh alfalfa (Medicago sativa) and tall fescue (Festuca arundinacea). Addition levels of 4% and 6% improved average body weight gain (BWG) by 215.71 and 142.86 g/d, and feed conversion ratio (FCR) by 0.20 and 0.14, respectively. Digestibility of dry matter (DM), organic matter (OM), neutral detergent fiber (NDF), and ether extract (EE) was 62.25%, 65.18%, 58.75%, and 47.25% under the addition level of 2%, which is greater than that in the control group. C. deserticola addition improved energy utilization efficiency, while addition levels of 2% and 4% increased nitrogen intake and deposited nitrogen. Overall, C. deserticola has the potential to improve growth performance, digestion of sheep, so it has suitability to be used as a feed additive.

Ten patients with high-grade transformation of acinic cell carcinomas: Expression profiling of ß-catenin and cyclin D1 is useful.

Conventional acinic cell carcinoma (CACC) represents a prototypical low-grade salivary malignancy. Rarely, acinic cell carcinoma (ACC) can demonstrate aggressive features (zones of necrosis, apoptosis, varying nuclear atypia) warranting classification as "ACC with high-grade transformation" (HGT-ACC) or "dedifferentiated" ACC. This study reports ten new cases of HGT-ACC. There is potential for subtlety in recognizing high-grade transformation and distinguishing discrete nodules of necrosis from cytology aspiration changes. We compared immunohistochemical (IHC) profiles, specifically ß-catenin (bCAT) and cyclin D1 expression, which have been touted as potentially helpful in this context. We quantified morphology (primary axis nucleus, nuclear area and perimeter) in HGT-ACC and CACC. Clinical outcome is known for eight HGT-ACC patients; three patients developed locoregional or distant metastases, five remained disease-free. Nine of ten HGT-ACC expressed strong, diffuse, membranous bCAT. CACC demonstrated lower intensity of membranous bCAT expression. Strong, diffuse nuclear cyclin D1 was seen in five of ten HGT-ACC whereas no CACC demonstrated cyclin D1 with distribution greater than 50 %. The quantified nuclear morphologic features of CACC and HGT-ACC demonstrated overlapping means values. Maximum values for nuclear primary axis, area, and perimeter were greater for HGT-ACC versus CACC, corresponding to a subpopulation of larger tumor cells in HGT-ACC. The poor outcome associated with HGT-ACC justifies its recognition, which should alter surgical approach with respect to elective neck dissection or possible facial nerve sacrifice. With respect to ancillary IHC studies, strong, diffuse membranous bCAT expression, with or without strong nuclear cyclin D1 ≥ 50 % distribution or Ki67 index ≥ 25 % supports this diagnosis.

Measuring Emergency Department Acuity.

BACKGROUND: Emergency department (ED) acuity is the general level of patient illness, urgency for clinical intervention, and intensity of resource use in an ED environment. The relative strength of commonly used measures of ED acuity is not well understood. METHODS: We performed a retrospective cross-sectional analysis of ED-level data to evaluate the relative strength of association between commonly used proxy measures with a full spectrum measure of ED acuity. Common measures included the percentage of patients with Emergency Severity Index (ESI) scores of 1 or 2, case mix index (CMI), academic status, annual ED volume, inpatient admission rate, percentage of Medicare patients, and patients seen per attending-hour. Our reference standard for acuity is the proportion of high-acuity charts (PHAC) coded and billed according to the Centers for Medicare and Medicaid Service's Ambulatory Payment Classification (APC) system. High-acuity charts included those APC 4 or 5 or critical care. PHAC was represented as a fractional response variable. We examined the strength of associations between common acuity measures and PHAC using Spearman's rank correlation coefficients (rs ) and regression models including a quasi-binomial generalized linear model and linear regression. RESULTS: In our univariate analysis, the percentage of patients ESI 1 or 2, CMI, academic status, and annual ED volume had statistically significant associations with PHAC. None explained more than 16% of PHAC variation. For regression models including all common acuity measures, academic status was the only variable significantly associated with PHAC. CONCLUSION: Emergency Severity Index had the strongest association with PHAC followed by CMI and annual ED volume. Academic status captures variability outside of that explained by ESI, CMI, annual ED volume, percentage of Medicare patients, or patients per attending per hour. All measures combined only explained only 42.6% of PHAC variation.