Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England.

BACKGROUND: The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission. METHODS: We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors. RESULTS: Compared with low intraoperative opioid dosing [quintile 1, median (inter-quartile range): 8 (4-9) mg morphine equivalents], exposure to high-dose opioids during surgery [quintile 5: 32 (27-41) equivalents] is an independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence interval 1.07-1.24); P<0.001]. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose-response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0-2 vs 3-30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors. CONCLUSIONS: High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery.

Association between intraoperative non-depolarising neuromuscular blocking agent dose and 30-day readmission after abdominal surgery.

BACKGROUND: We hypothesised that intraoperative non-depolarising neuromuscular blocking agent (NMBA) dose is associated with 30-day hospital readmission. METHODS: Data from 13,122 adult patients who underwent abdominal surgery under general anaesthesia at a tertiary care hospital were analysed by multivariable regression, to examine the effects of intraoperatively administered NMBA dose on 30-day readmission (primary endpoint), hospital length of stay, and hospital costs. RESULTS: Clinicians used cisatracurium (mean dose [SD] 0.19 mg kg-1 [0.12]), rocuronium (0.83 mg kg-1 [0.53]) and vecuronium (0.14 mg kg-1 [0.07]). Intraoperative administration of NMBAs was dose-dependently associated with higher risk of 30-day hospital readmission (adjusted odds ratio 1.89 [95% Confidence Interval (CI) 1.26-2.84] for 5th quintile vs 1st quintile; P for trend: P<0.001), prolonged hospital length of stay (adjusted incidence rate ratio [aIRR] 1.20 [95% CI 1.11-1.29]; P for trend: P<0.001) and increased hospital costs (aIRR 1.18 [95% CI 1.13-1.24]; P for trend: P<0.001). Admission type (same-day vs inpatient surgery) significantly modified the risk (interaction term: aOR 1.31 [95% CI 1.05-1.63], P=0.02), and the adjusted odds of readmission in patients undergoing ambulatory surgical procedures who received high-dose NMBAs vs low-dose NMBAs amounted to 2.61 [95% CI 1.11-6.17], P for trend: P<0.001. Total intraoperative neostigmine dose increased the risk of 30-day readmission (aOR 1.04 [1.0-1.08], P=0.048). CONCLUSIONS: In a retrospective analysis, high doses of NMBAs given during abdominal surgery was associated with an increased risk of 30-day readmission, particularly in patients undergoing ambulatory surgery.

Recognizing the long-term sequelae of burns as a chronic medical condition.

As medicine continues to advance, many individuals are living longer with injuries previously considered life threatening. These individuals often face numerous long-term physical and psychological sequelae associated with their injury that persist through the course of their lives. Recently, other injury populations have begun to think of their condition as "chronic". Using data collected from the Burn Model System National Database, a framework for the reconsideration of burn injury as a chronic condition is proposed.

The impact of electrical injuries on long-term outcomes: A Burn Model System National Database study.

INTRODUCTION: Electrical injuries exhibit significant acute and long-term sequelae. Amputation and neurological deficits are common in electrical injury survivors. There is a paucity of information on the long-term outcomes of this population. Therefore, this study examines the long-term outcomes of electrical injuries by comparing them to fire/flame injuries. METHODS: Data from the Burn Model System National Database collected between 1996 and 2015 was examined. Demographic and clinical characteristics for adult burn survivors with electrical and fire/flame injuries were compared. Satisfaction With Life Scale (SWLS), Short Form-12 Physical Composite Score (SF-12 PCS), Short Form-12 Mental Composite Score (SF-12 MCS), and employment status were examined at 24 months post-injury. Linear and logistic regression models were used to assess differences in outcome measures between groups, controlling for demographic and clinical variables. RESULTS: A total of 1147 adult burn survivors (111 with electrical injuries; 1036 with fire/flame injuries) were included in this study. Persons with electrical injuries were more likely to be male and injured at work (p<0.001). SF-12 PCS scores were significantly worse for survivors with electrical injuries at 24 months post-injury than survivors with fire/flame injuries (p<0.01). Those with electrical injuries were nearly half as likely to be employed at 24 months post-injury than those with fire/flame injuries (p=0.002). There were no significant differences in SWLS and SF-12 MCS between groups. CONCLUSIONS: Adult survivors with electrical injuries reported worse physical health and were less likely to be employed at 24 months post-injury compared to survivors with fire/flame injuries. A more detailed understanding of return to work barriers and work accommodations is merited for the electrical injury population. Furthermore, the results of this study should inform future resource allocation for the physical health and employment needs of this population.

Which symptom assessments and approaches are uniquely appropriate for paediatric concussion?

OBJECTIVE: To (a) identify post-concussion symptom scales appropriate for children and adolescents in sports; (b) review evidence for reliability and validity; and (c) recommend future directions for scale development. DESIGN: Quantitative and qualitative literature review of symptom rating scales appropriate for children and adolescents aged 5 to 22 years. INTERVENTION: Literature identified via search of Medline, Ovid-Medline and PsycInfo databases; review of reference lists in identified articles; querying sports concussion specialists. 29 articles met study inclusion criteria. RESULTS: 5 symptom scales examined in 11 studies for ages 5-12 years and in 25 studies for ages 13-22. 10 of 11 studies for 5-12-year-olds presented validity evidence for three scales; 7 studies provided reliability evidence for two scales; 7 studies used serial administrations but no reliable change metrics. Two scales included parent-reports and one included a teacher report. 24 of 25 studies for 13-22 year-olds presented validity evidence for five measures; seven studies provided reliability evidence for four measures with 18 studies including serial administrations and two examining Reliable Change. CONCLUSIONS: Psychometric evidence for symptom scales is stronger for adolescents than for younger children. Most scales provide evidence of concurrent validity, discriminating concussed and non-concussed groups. Few report reliability and evidence for validity is narrow. Two measures include parent/teacher reports. Few scales examine reliable change statistics, limiting interpretability of temporal changes. Future studies are needed to fully define symptom scale psychometric properties with the greatest need in younger student-athletes.

Head and neck burns are associated with long-term patient-reported dissatisfaction with appearance: A Burn Model System National Database study.

INTRODUCTION: Burns affecting the head and neck (H&N) can lead to significant changes in appearance. It is postulated that such injuries have a negative impact on patients' social functioning, quality of life, physical health, and satisfaction with appearance, but there has been little investigation of these effects using patient reported outcome measures. This study evaluates the effect of H&N burns on long-term patient reported outcomes compared to patients who sustained burns to other areas. METHODS: Data from the National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System National Database collected between 1996 and 2015 were used to investigate differences in outcomes between those with and without H&N burns. Demographic and clinical characteristics for adult burn survivors with and without H&N burns were compared. The following patient-reported outcome measures, collected at 6, 12, and 24 months after injury, were examined: satisfaction with life (SWL), community integration questionnaire (CIQ), satisfaction with appearance (SWAP), short form-12 physical component score (SF-12 PCS), and short form-12 mental component score (SF-12 MCS). Mixed regression model analyses were used to examine the associations between H&N burns and each outcome measure, controlling for medical and demographic characteristics. RESULTS: A total of 697 adults (373 with H&N burns; 324 without H&N burns) were included in the analyses. Over 75% of H&N injuries resulted from a fire/flame burn and those with H&N burns had significantly larger burn size (p<0.001). In the mixed model regression analyses, SWAP and SF-12 MCS were significantly worse for adults with H&N burns compared to those with non-H&N burns (p<0.01). There were no significant differences between SWL, CIQ, and SF-12 PCS. CONCLUSIONS: Survivors with H&N burns demonstrated community integration, physical health, and satisfaction with life outcomes similar to those of survivors with non-H&N burns. Scores in these domains improved over time. However, survivors with H&N burns demonstrated worse satisfaction with their appearance. These results suggest that strategies to address satisfaction with appearance, such as reconstructive surgery, cognitive behavior therapy, and social skills training, are an area of need for survivors with H&N burns.

Regulation of the yeast CYT1 gene encoding cytochrome c1 by HAP1 and HAP2/3/4.

Mitochondrial biogenesis requires the coordinate induction of hundreds of genes that reside in the nucleus. We describe here a study of the regulation of the nuclear-encoded cytochrome c1 of the b-c1 complex. Unlike cytochrome c, which is encoded by two genes, CYC1 and CYC7, c1 is encoded by a single gene, CYT1. The regulatory region of the CYT1 promoter contains binding sites for the HAP1 and HAP2/3/4 transactivators that regulate CYC1. The binding of HAP1 to the CYT1 element was studied in detail and found to differ in two important respects from binding to the CYC1 element. First, while CYC1 contains two sites that bind HAP1 cooperatively, CYT1 has a single high-affinity site. Second, while the CYT1 site and the stronger HAP1-binding site of CYC1 share a large block of homology, the HAP1 footprints at these sites are offset by several nucleotides. We discuss how these differences in HAP1 binding might relate to the difference in the biology of cytochrome c and cytochrome c1.

Satisfaction with life after burn: A Burn Model System National Database Study.

OBJECTIVES: While mortality rates after burn are low, physical and psychosocial impairments are common. Clinical research is focusing on reducing morbidity and optimizing quality of life. This study examines self-reported Satisfaction With Life Scale scores in a longitudinal, multicenter cohort of survivors of major burns. Risk factors associated with Satisfaction With Life Scale scores are identified. METHODS: Data from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) Burn Model System (BMS) database for burn survivors greater than 9 years of age, from 1994 to 2014, were analyzed. Demographic and medical data were collected on each subject. The primary outcome measures were the individual items and total Satisfaction With Life Scale (SWLS) scores at time of hospital discharge (pre-burn recall period) and 6, 12, and 24 months after burn. The SWLS is a validated 5-item instrument with items rated on a 1-7 Likert scale. The differences in scores over time were determined and scores for burn survivors were also compared to a non-burn, healthy population. Step-wise regression analysis was performed to determine predictors of SWLS scores at different time intervals. RESULTS: The SWLS was completed at time of discharge (1129 patients), 6 months after burn (1231 patients), 12 months after burn (1123 patients), and 24 months after burn (959 patients). There were no statistically significant differences between these groups in terms of medical or injury demographics. The majority of the population was Caucasian (62.9%) and male (72.6%), with a mean TBSA burned of 22.3%. Mean total SWLS scores for burn survivors were unchanged and significantly below that of a non-burn population at all examined time points after burn. Although the mean SWLS score was unchanged over time, a large number of subjects demonstrated improvement or decrement of at least one SWLS category. Gender, TBSA burned, LOS, and school status were associated with SWLS scores at 6 months; scores at 12 months were associated with LOS, school status, and amputation; scores at 24 months were associated with LOS, school status, and drug abuse. CONCLUSIONS: In this large, longitudinal, multicenter cohort of burn survivors, satisfaction with life after burn was consistently lower than that of non-burn norms. Furthermore mean SWLS scores did not improve over the two-year follow-up period. This study demonstrates the need for continued efforts to improve patient-centered long term satisfaction with life after burn.

A double-labelling fluorescent assay for concomitant measurements of [Ca2+]i and O2. production in human macrophages.

To measure intracellular free Ca2+ concentration ([Ca2+]i) and superoxide (O2) production in human alveolar macrophages, we used the fluorescent Ca2+ indicator fura-2 and the O2-sensitive dye dihydrorhodamine-123, which becomes fluorescent in its oxidized form, rhodamine-123. We describe a new double-dye technique whereby the kinetics of both [Ca2+]i levels and O2. production can be monitored simultaneously. This technique was developed in the dimethylsulfoxide-differentiated monocytic-like U-937 cell line (not equal to U-937), validated by comparison with single dye measurements and applied to human alveolar macrophages. The chemotactic peptide N-formyl-L-Methionyl-L-Leucyl-L-Phenylalanine induced in both cell types a similar transient elevation in [Ca2+]i, followed within seconds by a sustained increase in O2 production, which was however 4-fold weaker in not equal to U-937 cells. These results indicate that O2 production is an early event following the stimulation of human alveolar macrophages. This new double-dye technique may be relevant to other O2 ion-producing cells and could help to define more precisely the kinetics of the events leading to this biological response.

Operation Everest III: role of plasma volume expansion on VO(2)(max) during prolonged high-altitude exposure.

We hypothesize that plasma volume decrease (DeltaPV) induced by high-altitude (HA) exposure and intense exercise is involved in the limitation of maximal O(2) uptake (VO(2)(max)) at HA. Eight male subjects were decompressed for 31 days in a hypobaric chamber to the barometric equivalent of Mt. Everest (8,848 m). Maximal exercise was performed with and without plasma volume expansion (PVX, 219-292 ml) during exercise, at sea level (SL), at HA (370 mmHg, equivalent to 6, 000 m after 10-12 days) and after return to SL (RSL, 1-3 days). Plasma volume (PV) was determined at rest at SL, HA, and RSL by Evans blue dilution. PV was decreased by 26% (P < 0.01) at HA and was 10% higher at RSL than at SL. Exercise-induced DeltaPV was reduced both by PVX and HA (P < 0.05). Compared with SL, VO(2)(max) was decreased by 58 and 11% at HA and RSL, respectively. VO(2)(max) was enhanced by PVX at HA (+9%, P < 0.05) but not at SL or RSL. The more PV was decreased at HA, the more VO(2)(max) was improved by PVX (P < 0.05). At exhaustion, plasma renin and aldosterone were not modified at HA compared with SL but were higher at RSL, whereas plasma atrial natriuretic factor was lower at HA. The present results suggest that PV contributes to the limitation of VO(2)(max) during acclimatization to HA. RSL-induced PVX, which may be due to increased activity of the renin-aldosterone system, could also influence the recovery of VO(2)(max).

Operation Everest III (COMEX '97). Effects of prolonged and progressive hypoxia on humans during a simulated ascent to 8,848 M in a hypobaric chamber.

Exposure to high altitude induces physiological or pathological modifications that are not always clearly attributable to a specific environmental factor: hypoxia, cold, stress, inadequate food. The principal goal of hypobaric chamber studies is to determine the specific effect of hypoxia. Eight male volunteers ("altinauts"), aged 23 to 37 were selected. They were first preacclimatized in the Observatoire Vallot (4,350 m) before entering the chamber. The chamber was progressively decompressed down to 253 mmHg barometric pressure, with a recovery period of 3 days at 5,000 m in the middle of the decompression period. They spent a total of 31 days in the chamber. Eighteen protocols were organized by 14 European teams, exploring the limiting factors of physical and psychological performance, and the pathophysiology of acute mountain sickness (AMS). All subjects reached 8,000 m and 7 of them reached the simulated altitude of 8,848 m. Three altinauts complained of transient neurological symptoms which resolved rapidly with reoxygenation. Body weight decreased by 5.4 kg through a negative caloric balance. Only four days after the return to sea-level, subjects had recovered 3.4 kg, i.e. 63% of the total loss. At 8,848 m (n = 5), PaO2 was 30.6 +/- 1.4 mmHg, PCO2 11.9 +/- 1.4 mmHg, pH 7.58 +/- 0.02 (arterialized capillary blood). Hemoglobin concentration increased from 14.8 +/- 1.4 to 18.4 +/- 1.5 g/dl at 8,000 m and recovered within 4 days at sea-level. AMS score increased rapidly at 6,000 m and was maximal at 7,000 m, especially for sleep. AMS was related to alteration in color vision and elevation of body temperature. VO2MAX decreased by 59% at 7,000 m. The purpose of this paper is to give a general description of the study and the time course of the main clinical and physiological parameters. The altinauts reached the "summit" (for some of them three consecutive times) in better physiological conditions than it would have been possible in the mountains, probably because acclimatization and other environmental factors such as cold and nutrition were controlled.