Use of mechanical ventilation protocols in intensive care units: a survey of current practice.

INTRODUCTION: Mechanical ventilation protocols for treating intensive care unit (ICU) patients are often recommended to improve process of care and outcomes, but their composition may be variable and penetration into clinical practice may be incomplete. We sought to ascertain ICU and hospital characteristics associated with adoption of mechanical ventilation (MV) protocols in Ontario, Canada. METHODS: We surveyed respiratory therapy leaders in all 97 Ontario hospitals capable of providing MV in an ICU. RESULTS: We received responses from 70 hospitals (72.2%). Two-thirds (46/67; 68.7%) of hospitals reported having a respiratory therapist on duty 24 hours/7 days per week. Mechanical ventilation protocols were present in most hospitals (47/67; 70.2%), but low tidal volume ventilation was incorporated into only half of these protocols (24/44; 54.5%). Factors associated with reported use of MV protocols were intensivist-staffing model (89.3% vs 56.4%; odds ratio [OR], 6.44; [95% confidence interval {CI}, 1.66-25.0; P = .007]), presence of daily multidisciplinary rounds (84.4% vs 42.9%; OR, 7.24 [95% CI, 2.22-23.6; P = .001]), and presence of 24 hour/7 days per week respiratory therapist coverage (87.0% vs 36.4%; OR, 11.7 [95% CI, 3.44-39.6; P < .001]). The likelihood of having an MV protocol also increased with increasing patient-to-physician ratio (OR for each increase of 1 patient, 1.17 [95% CI, 1.01-1.35; P = .034] and increasing ICU size (OR for each additional ICU bed, 1.05 [95% CI, 1.00-1.10; P = .04]). CONCLUSION: Most surveyed hospitals reported the presence of a protocol for MV, but only half of these incorporated low tidal volume ventilation. Several organizational factors were associated with adoption of protocols, and therefore, these should also be considered when evaluating the impact of protocols on clinical outcomes.

Pilot candidate gene analysis of patients ≥ 60 years old with aortic stenosis involving a tricuspid aortic valve.

The potential genetic basis of aortic stenosis in older people is poorly understood. A total of 265 patients with aortic stenosis involving tricuspid aortic valves and 961 controls were genotyped for ≤660 candidate single nucleotide polymorphisms (SNPs). After dividing the patients and controls into training and validation sets, we tested the correlation of the SNPs with the age-adjusted aortic valve area, determined by echocardiography or cardiac catheterization. A bootstrapped global p value of ≤0.005 was considered evidence of a possible significant correlation. The cases were aged 73 ± 7 years, and 72.7% were men. The median aortic valve area was 1.0 cm(2) (interquartile range 0.7 to 1.5). The controls were aged 69 ± 6 years, and 69.8% were men. The minor allele frequency was 21% ± 15% (37% <0.20). Three SNPs met the criteria for significant correlation (rs2276288 [MYO7A], p = 0.001; rs5194 [AGTR1], p = 0.004; rs207 307 [ELN], p = 0.005). Another 2 SNPs reached borderline significance (p ≤0.008). In conclusion, we report 3 SNPs to be associated with aortic stenosis involving tricuspid aortic valves in older subjects. Given the concerns regarding the problem of multiple statistical testing, validation studies are required to further assess these correlations.

Compressive sensing-based interior tomography: preliminary clinical application.

Compressive sensing (CS)-based interior tomography is a state-of-the-art method for accurate image reconstruction from only locally truncated projections. Here, we report our preliminary interior tomography results reconstructed from raw projections of a patient acquired on a GE Discovery CT750 HD scanner. This is the first clinical application of the CS-based interior reconstruction techniques, and the results show an excellent match with those reconstructed from global projections.

Enhanced prediction of mortality after percutaneous coronary intervention by consideration of general and neurological indicators.

OBJECTIVES: This study sought to improve methodology for predicting post-percutaneous coronary intervention (PCI) mortality. BACKGROUND: Recently, an increased proportion of post-PCI deaths caused by noncardiac causes has been suggested, often in rapidly triaged patients resuscitated from sudden cardiac death or presenting with cardiogenic shock. Older risk adjustment algorithms may not adequately reflect these issues. METHODS: Consecutive patients undergoing PCI from 2000 to 2009 were randomly divided into training (n = 8,966) and validation (n = 8,891) cohorts. The 2010 ACC-NCDR (American College of Cardiology-National Cardiovascular Data Registry) mortality algorithm was applied to the training cohort and its highest risk decile, separately. Variables describing general and neurological status at admission were then tested for their additional predictive capability and new algorithms developed. These were tested in the validation cohort, using receiver-operator characteristic curve, Hosmer-Lemeshow, and reclassification measures as principal outcome measures. RESULTS: In-hospital mortality was 1.0%, of which 52.2% had noncardiac causes or major contributions. Baseline model C-statistics for the total and upper decile training cohorts were 0.904 and 0.830. The Aldrete score (addressing consciousness, respiration, skin color, muscle function, and circulation) and neurology scores added incremental information, resulting in improved validation cohort C-statistics (entire group: 0.883 to 0.914, p < 0.001; high-risk decile: 0.829 to 0.874, p < 0.001). Reclassification of the ACC-NCDR <90th and ≥90th risk percentiles by the new score yielded improved mortality prediction (p < 0.001 and p = 0.033, respectively). CONCLUSIONS: Half of in-hospital deaths in this series were of noncardiac causation. Prediction of in-hospital mortality after PCI can be considerably improved over conventional models by the inclusion of variables describing general and neurological status.

Effects of environmental exposure and diet on levels of persistent organic pollutants (POPs) in eggs of a top predator in the North Atlantic in 1980 and 2008.

Concentrations of POPs in Great skua eggs from Shetland are among the highest in North Atlantic seabirds, with up to 11,600 µg/kg (ww) DDE and up to 17,900 µg/kg ww ∑PCB. Concentrations of legacy POPs were significantly lower in 2008 than 1980. Decreases were greatest for least persistent compounds. Median ∑PBDEs increased from 99 µg/kg ww in 1980 to 173 µg/kg ww in 2008. There were changes in Great skua breeding season diet, with more adult Herring and Mackerel and less Sandeel. These changes increase exposure to POPs, since Herring and Mackerel accumulate more POPs than Sandeels. In both years, eggs with higher δ15N had higher POP concentrations. In 1980, birds feeding more on demersal discard fish from trawl fisheries and less on Sandeels, had higher POP levels in eggs. In 2008, individuals feeding more on Herring and Mackerel, and less on discards, had higher POP levels in eggs.

Identifying the source of species invasions: sampling intensity vs. genetic diversity.

Population geneticists and community ecologists have long recognized the importance of sampling design for uncovering patterns of diversity within and among populations and in communities. Invasion ecologists increasingly have utilized phylogeographical patterns of mitochondrial or chloroplast DNA sequence variation to link introduced populations with putative source populations. However, many studies have ignored lessons from population genetics and community ecology and are vulnerable to sampling errors owing to insufficient field collections. A review of published invasion studies that utilized mitochondrial or chloroplast DNA markers reveals that insufficient sampling could strongly influence results and interpretations. Sixty per cent of studies sampled an average of less than six individuals per source population, vs. only 45% for introduced populations. Typically, far fewer introduced than source populations were surveyed, although they were sampled more intensively. Simulations based on published data forming a comprehensive mtDNA haplotype data set highlight and quantify the impact of the number of individuals surveyed per source population and number of putative source populations surveyed for accurate assignment of introduced individuals. Errors associated with sampling a low number of individuals are most acute when rare source haplotypes are dominant or fixed in the introduced population. Accuracy of assignment of introduced individuals is also directly related to the number of source populations surveyed and to the degree of genetic differentiation among them (F(ST)). Incorrect interpretations resulting from sampling errors can be avoided if sampling design is considered before field collections are made.

Peptide YY3-36 and glucagon-like peptide-17-36 inhibit food intake additively.

Peptide YY (PYY) and glucagon like peptide (GLP)-1 are cosecreted from intestinal L cells, and plasma levels of both hormones rise after a meal. Peripheral administration of PYY(3-36) and GLP-1(7-36) inhibit food intake when administered alone. However, their combined effects on appetite are unknown. We studied the effects of peripheral coadministration of PYY(3-36) with GLP-1(7-36) in rodents and man. Whereas high-dose PYY(3-36) (100 nmol/kg) and high-dose GLP-1(7-36) (100 nmol/kg) inhibited feeding individually, their combination led to significantly greater feeding inhibition. Additive inhibition of feeding was also observed in the genetic obese models, ob/ob and db/db mice. At low doses of PYY(3-36) (1 nmol/kg) and GLP-1(7-36) (10 nmol/kg), which alone had no effect on food intake, coadministration led to significant reduction in food intake. To investigate potential mechanisms, c-fos immunoreactivity was quantified in the hypothalamus and brain stem. In the hypothalamic arcuate nucleus, no changes were observed after low-dose PYY(3-36) or GLP-1(7-36) individually, but there were significantly more fos-positive neurons after coadministration. In contrast, there was no evidence of additive fos-stimulation in the brain stem. Finally, we coadministered PYY(3-36) and GLP-1(7-36) in man. Ten lean fasted volunteers received 120-min infusions of saline, GLP-1(7-36) (0.4 pmol/kg.min), PYY(3-36) (0.4 pmol/kg.min), and PYY(3-36) (0.4 pmol/kg.min) + GLP-1(7-36) (0.4 pmol/kg.min) on four separate days. Energy intake from a buffet meal after combined PYY(3-36) + GLP-1(7-36) treatment was reduced by 27% and was significantly lower than that after either treatment alone. Thus, PYY(3-36) and GLP-1(7-36), cosecreted after a meal, may inhibit food intake additively.

Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial.

This study investigated the effect of subcutaneously administered oxyntomodulin on body weight in healthy overweight and obese volunteers. Participants self-administered saline or oxyntomodulin subcutaneously in a randomized, double-blind, parallel-group protocol. Injections were self-administered for 4 weeks, three times daily, 30 min before each meal. The volunteers were asked to maintain their regular diet and level of physical exercise during the study period. Subjects' body weight, energy intake, and levels of adipose hormones were assessed at the start and end of the study. Body weight was reduced by 2.3 +/- 0.4 kg in the treatment group over the study period compared with 0.5 +/- 0.5 kg in the control group (P = 0.0106). On average, the treatment group had an additional 0.45-kg weight loss per week. The treatment group demonstrated a reduction in leptin and an increase in adiponectin. Energy intake by the treatment group was significantly reduced by 170 +/- 37 kcal (25 +/- 5%) at the initial study meal (P = 0.0007) and by 250 +/- 63 kcal (35 +/- 9%) at the final study meal (P = 0.0023), with no change in subjective food palatability. Oxyntomodulin treatment resulted in weight loss and a change in the levels of adipose hormones consistent with a loss of adipose tissue. The anorectic effect was maintained over the 4-week period. Oxyntomodulin represents a potential therapy for obesity.

Real-world bare metal stenting: identification of patients at low or very low risk of 9-month coronary revascularization.

The high cost of drug-eluting stents (DESs) has made identification of patients who are at low risk for subsequent revascularization after treatment with bare metal stents (BMSs) highly desirable. Previous reports from randomized trials suffer from biases induced by restricted entry criteria and protocol-mandated angiographic follow-up. Between 1994 and 2001, 5,239 consecutive BMS patients, excluding those with coil stents, technical failure, brachytherapy, staged procedure, or stent thrombosis within 30 days, were prospectively identified from a large single-center tertiary-referral-center prospective registry for long-term follow-up. We sought to identify characteristics of patients with very low (< or = 4%) or low (4-10%) likelihood of coronary revascularization 9 months after BMS. Nine-month clinical follow-up was obtained in 98.2% of patients. Coronary revascularization was required in 13.4% and did not differ significantly by stent type. On the basis of multivariate analysis identifying 11 independent correlates and previous reports, 20 potential low-risk patient and lesion groups (228 +/- 356 patients/groups) were identified (e.g, patients with all of the following: native vessel, de novo, reference diameter > or = 3.5 mm, lesion length < 5 mm, no diabetes, not ostial in location). Actual and model-based outcomes were analyzed. No group had both predicted and observed 9-month revascularization < or = 4% (very low risk). Conversely, 19 of 20 groups had a predicted and observed revascularization rate of 4-10% (low risk). In the real-world setting, the need for intermediate-term revascularization after BMS may be lower than expected, but it may be very difficult to identify patients at very low risk. Conversely, if the benefits of DESs are attenuated in routine practice, many groups of patients treated with BMSs may have nearly comparable results.

Oxyntomodulin suppresses appetite and reduces food intake in humans.

Oxyntomodulin (OXM) is released from the gut postprandially, in proportion to energy intake, and circulating levels of OXM are elevated in several conditions associated with anorexia. Central injection of OXM reduces food intake and weight gain in rodents, suggesting that OXM signals food ingestion to hypothalamic appetite-regulating circuits. We investigated the effect of iv OXM (3.0 pmol/kg.min) on appetite and food intake in 13 healthy subjects (body mass index, 22.5 +/- 0.9 kg/m(2)) in a randomized, double-blind, placebo-controlled, cross-over study. Infusion of OXM significantly reduced ad libitum energy intake at a buffet meal (mean decrease, 19.3 +/- 5.6%; P < 0.01) and caused a significant reduction in scores for hunger. In addition, cumulative 12-h energy intake was significantly reduced by infusion of OXM (mean decrease, 11.3 +/- 6.2%; P < 0.05). OXM did not cause nausea or affect food palatability. Preprandial levels of the appetite-stimulatory hormone, ghrelin, were significantly suppressed by OXM (mean reduction, 44 +/- 10% of postprandial decrease; P < 0.0001). Elevated levels of endogenous OXM associated with disorders of the gastrointestinal tract may contribute to anorexia.

Inhibition of food intake in obese subjects by peptide YY3-36.

BACKGROUND: The gut hormone fragment peptide YY3-36 (PYY) reduces appetite and food intake when infused into subjects of normal weight. In common with the adipocyte hormone leptin, PYY reduces food intake by modulating appetite circuits in the hypothalamus. However, in obesity there is a marked resistance to the action of leptin, which greatly limits its therapeutic effectiveness. We investigated whether obese subjects were also resistant to the anorectic effects of PYY. METHODS: We compared the effects of PYY infusion on appetite and food intake in 12 obese and 12 lean subjects in a double-blind, placebo-controlled, crossover study. The plasma levels of PYY, ghrelin, leptin, and insulin were also determined. RESULTS: Caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in the obese subjects (P<0.001) and 31 percent in the lean subjects (P<0.001). PYY infusion also caused a significant decrease in the cumulative 24-hour caloric intake in both obese and lean subjects. PYY infusion reduced plasma levels of the appetite-stimulatory hormone ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects (the mean [+/-SE] fasting PYY levels were 10.2+/-0.7 pmol per liter in the obese group and 16.9+/-0.8 pmol per liter in the lean group, P<0.001). Furthermore, the fasting PYY levels correlated negatively with the body-mass index (r = -0.84, P<0.001). CONCLUSIONS: We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity.

Central overweight and obesity in British youth aged 11-16 years: cross sectional surveys of waist circumference.

OBJECTIVE: To compare changes over time in waist circumference (a measure of central fatness) and body mass index (a measure of overall obesity) in British youth. DESIGN: Representative cross sectional surveys in 1977, 1987, and 1997. SETTING: Great Britain. PARTICIPANTS: Young people aged 11-16 years surveyed in 1977 (boys) and 1987 (girls) for the British Standards Institute (n=3784) and in 1997 (both sexes) for the national diet and nutrition survey (n=776). MAIN OUTCOME MEASURES: Waist circumference, expressed as a standard deviation score using the first survey as reference, and body mass index (weight(kg)/height(m)2), expressed as a standard deviation score against the British 1990 revised reference. Overweight and obesity were defined as the measurement exceeding the 91st and 98th centile, respectively. RESULTS: Waist circumference increased sharply over the period between surveys (mean increases for boys and girls, 6.9 and 6.2 cm, or 0.84 and 1.02 SD score units, P<0.0001). In centile terms, waist circumference increased more in girls than in boys. Increases in body mass index were smaller and similar by sex (means 1.5 and 1.6, or 0.47 and 0.53 SD score units, P<0.0001). Waist circumference in 1997 exceeded the 91st centile in 28% (n=110) of boys and 38% (n=147) of girls (against 9% for both sexes in 1977-87, P<0.0001), whereas 14% (n=54) and 17% (n=68), respectively, exceeded the 98th centile (3% in 1977-87, P<0.0001). The corresponding rates for body mass index in 1997 were 21% (n=80) of boys and 17% (n=67) of girls exceeding the 91st centile (8% and 6% in 1977-87) and 10% (n=39) and 8% (n=32) exceeding the 98th centile (3% and 2% in 1977-87). CONCLUSIONS: Trends in waist circumference during the past 10-20 years have greatly exceeded those in body mass index, particularly in girls, showing that body mass index is a poor proxy for central fatness. Body mass index has therefore systematically underestimated the prevalence of obesity in young people.