Flash monitor initiation is associated with improvements in HbA1c levels and DKA rates among people with type 1 diabetes in Scotland: a retrospective nationwide observational study.

AIMS/HYPOTHESIS: We assessed the real-world effect of flash monitor (FM) usage on HbA1c levels and diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH) rates among people with type 1 diabetes in Scotland and across sociodemographic strata within this population. METHODS: This study was retrospective, observational and registry based. Using the national diabetes registry, 14,682 individuals using an FM at any point between 2014 and mid-2020 were identified. Within-person change from baseline in HbA1c following FM initiation was modelled using linear mixed models accounting for within-person pre-exposure trajectory. DKA and SHH events were captured through linkage to hospital admission and mortality data. The difference in DKA and SHH rates between FM-exposed and -unexposed person-time was assessed among users, using generalised linear mixed models with a Poisson likelihood. In a sensitivity analysis, we tested whether changes in these outcomes were seen in an age-, sex- and baseline HbA1c-matched sample of non-users over the same time period. RESULTS: Prevalence of ever-FM use was 45.9% by mid-2020, with large variations by age and socioeconomic status: 64.3% among children aged <13 years vs 32.7% among those aged ≥65 years; and 54.4% vs 36.2% in the least-deprived vs most-deprived quintile. Overall, the median (IQR) within-person change in HbA1c in the year following FM initiation was -2.5 (-9.0, 2.5) mmol/mol (-0.2 [-0.8, 0.2]%). The change varied widely by pre-usage HbA1c: -15.5 (-31.0, -4.0) mmol/mol (-1.4 [-2.8, -0.4]%) in those with HbA1c > 84 mmol/mol [9.8%] and 1.0 (-2.0, 5.5) mmol/mol (0.1 [-0.2, 0.5]%) in those with HbA1c < 54 mmol/mol (7.1%); the corresponding estimated fold change (95% CI) was 0.77 (0.76, 0.78) and 1.08 (1.07, 1.09). Significant reductions in HbA1c were found in all age bands, sexes and socioeconomic strata, and regardless of prior/current pump use, completion of a diabetes education programme or early FM adoption. Variation between the strata of these factors beyond that driven by differing HbA1c at baseline was slight. No change in HbA1c in matched non-users was observed in the same time period (median [IQR] within-person change = 0.5 [-5.0, 5.5] mmol/mol [0.0 (-0.5, 0.5)%]). DKA rates decreased after FM initiation overall and in all strata apart from the adolescents. Estimated overall reduction in DKA event rates (rate ratio) was 0.59 [95% credible interval (CrI) 0.53, 0.64]) after FM vs before FM initiation, accounting for pre-exposure trend. Finally, among those at higher risk for SHH, estimated reduction in event rates was rate ratio 0.25 (95%CrI 0.20, 0.32) after FM vs before FM initiation. CONCLUSIONS/INTERPRETATION: FM initiation is associated with clinically important reductions in HbA1c and striking reduction in DKA rate. Increasing uptake among the socioeconomically disadvantaged offers considerable potential for tightening the current socioeconomic disparities in glycaemia-related outcomes.

Effect of Intraoperative Handovers of Anesthesia Care on Mortality, Readmission, or Postoperative Complications Among Adults: The HandiCAP Randomized Clinical Trial.

Importance: Intraoperative handovers of anesthesia care are common. Handovers might improve care by reducing physician fatigue, but there is also an inherent risk of losing critical information. Large observational analyses report associations between handover of anesthesia care and adverse events, including higher mortality. Objective: To determine the effect of handovers of anesthesia care on postoperative morbidity and mortality. Design, Setting, and Participants: This was a parallel-group, randomized clinical trial conducted in 12 German centers with patients enrolled between June 2019 and June 2021 (final follow-up, July 31, 2021). Eligible participants had an American Society of Anesthesiologists physical status 3 or 4 and were scheduled for major inpatient surgery expected to last at least 2 hours. Interventions: A total of 1817 participants were randomized to receive either a complete handover to receive anesthesia care by another clinician (n = 908) or no handover of anesthesia care (n = 909). None of the participating institutions used a standardized handover protocol. Main Outcomes and Measures: The primary outcome was a 30-day composite of all-cause mortality, hospital readmission, or serious postoperative complications. There were 19 secondary outcomes, including the components of the primary composite, along with intensive care unit and hospital lengths of stay. Results: Among 1817 randomized patients, 1772 (98%; mean age, 66 [SD, 12] years; 997 men [56%]; and 1717 [97%] with an American Society of Anesthesiologists physical status of 3) completed the trial. The median total duration of anesthesia was 267 minutes (IQR, 206-351 minutes), and the median time from start of anesthesia to first handover was 144 minutes in the handover group (IQR, 105-213 minutes). The composite primary outcome occurred in 268 of 891 patients (30%) in the handover group and in 284 of 881 (33%) in the no handover group (absolute risk difference [RD], -2.5%; 95% CI, -6.8% to 1.9%; odds ratio [OR], 0.89; 95% CI, 0.72 to 1.10; P = .27). Nineteen of 889 patients (2.1%) in the handover group and 30 of 873 (3.4%) in the no handover group experienced all-cause 30-day mortality (absolute RD, -1.3%; 95% CI, -2.8% to 0.2%; OR, 0.61; 95% CI, 0.34 to 1.10; P = .11); 115 of 888 (13%) vs 136 of 872 (16%) were readmitted to the hospital (absolute RD, -2.7%; 95% CI, -5.9% to 0.6%; OR, 0.80; 95% CI, 0.61 to 1.05; P = .12); and 195 of 890 (22%) vs 189 of 874 (22%) experienced serious postoperative complications (absolute RD, 0.3%; 95% CI, -3.6% to 4.1%; odds ratio, 1.02; 95% CI, 0.81 to 1.28; P = .91). None of the 19 prespecified secondary end points differed significantly. Conclusions and Relevance: Among adults undergoing extended surgical procedures, there was no significant difference between the patients randomized to receive handover of anesthesia care from one clinician to another, compared with the no handover group, in the composite primary outcome of mortality, readmission, or serious postoperative complications within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04016454.

The association of polypharmacy and high-risk drug classes with adverse health outcomes in the Scottish population with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this work was to map the number of prescribed drugs over age, sex and area-based socioeconomic deprivation, and to examine the association between the number of drugs and particular high-risk drug classes with adverse health outcomes among a national cohort of individuals with type 1 diabetes. METHODS: Utilising linked healthcare records from the population-based diabetes register of Scotland, we identified 28,245 individuals with a diagnosis of type 1 diabetes on 1 January 2017. For this population, we obtained information on health status, predominantly reflecting diabetes-related complications, and information on the total number of drugs and particular high-risk drug classes prescribed. We then studied the association of these baseline-level features with hospital admissions for falls, diabetic ketoacidosis (DKA), and hypoglycaemia or death within the subsequent year using multivariate Cox proportional hazards models. RESULTS: Not considering insulin and treatment for hypoglycaemia, the mean number of prescribed drugs was 4.00 (SD 4.35). The proportion of individuals being prescribed five or more drugs at baseline consistently increased with age (proportion [95% CI]: 0-19 years 2.04% [1.60, 2.49]; 40-49 years 28.50% [27.08, 29.93]; 80+ years 76.04% [67.73, 84.84]). Controlling for age, sex, area-based socioeconomic deprivation and health status, each additional drug at baseline was associated with an increase in the hazard for hospitalisation for falls, hypoglycaemia and death but not for DKA admissions (HR [95% CI]: falls 1.03 [1.01, 1.06]; DKA 1.01 [1.00, 1.03]; hypoglycaemia 1.05 [1.02, 1.07]; death 1.04 [1.02, 1.06]). We found a number of drug classes to be associated with an increased hazard of one or more of these adverse health outcomes, including antithrombotic/anticoagulant agents, corticosteroids, opioids, antiepileptics, antipsychotics, hypnotics and sedatives, and antidepressants. CONCLUSIONS: Polypharmacy is common among the Scottish population with type 1 diabetes and is strongly patterned by sociodemographic factors. The number of prescribed drugs and the prescription of particular high-risk drug classes are strong markers of an increased risk of adverse health outcomes, including acute complications of diabetes.

Marked improvements in glycaemic outcomes following insulin pump therapy initiation in people with type 1 diabetes: a nationwide observational study in Scotland.

AIMS/HYPOTHESIS: Our aim was to assess the use of continuous subcutaneous insulin infusion (CSII) in people with type 1 diabetes in Scotland and its association with glycaemic control, as measured by HbA1c levels, frequency of diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH), overall and stratified by baseline HbA1c. METHODS: We included 4684 individuals with type 1 diabetes from the national Scottish register, who commenced CSII between 2004 and 2019. We presented crude within-person differences from baseline HbA1c over time since initiation, crude DKA and SHH event-rates pre-/post-CSII exposure. We then used mixed models to assess the significance of CSII exposure, taking into account: (1) the diffuse nature of the intervention (i.e. structured education often precedes initiation); (2) repeated within-person measurements; and (3) background time-trends occurring pre-intervention. RESULTS: HbA1c decreased after CSII initiation, with a median within-person change of -5.5 mmol/mol (IQR -12.0, 0.0) (-0.5% [IQR -1.1, 0.0]). Within-person changes were most substantial in those with the highest baseline HbA1c, with median -21.0 mmol/mol (-30.0, -11.0) (-1.9% [-2.7, -1.0]) change in those with a baseline >84 mmol/mol (9.8%) within a year of exposure, that was sustained: -19.0 mmol/mol (-27.6, -6.5) (-1.7% [-2.5, -0.6]) at ≥5 years. Statistical significance and magnitude of change were supported by the mixed models results. The crude DKA event-rate was significantly lower in post-CSII person-time compared with pre-CSII person-time: 49.6 events (95% CI 46.3, 53.1) per 1000 person-years vs 67.9 (64.1, 71.9); rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.61 (95% credible interval [CrI] 0.47, 0.77; posterior probability of reduction pp = 1.00). The crude overall SHH event-rate in post-CSII vs pre-CSII person-time was also lower: 17.8 events (95% CI 15.8, 19.9) per 1000 person-years post-exposure vs 25.8 (23.5, 28.3) pre-exposure; rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.67 (95% CrI 0.45, 1.01; pp = 0.97). CONCLUSIONS/INTERPRETATION: CSII therapy was associated with marked falls in HbA1c especially in those with high baseline HbA1c. CSII was independently associated with reduced DKA and SHH rates. CSII appears to be an effective option for intensive insulin therapy in people with diabetes for improving suboptimal glycaemic control.

Rethinking morbidity compression.

Studies of morbidity compression routinely report the average number of years spent in an unhealthy state but do not report variation in age at morbidity onset. Variation was highlighted by Fries (1980) as crucial for identifying disease postponement. Using incidence of first hospitalization after age 60, as one working example, we estimate variation in morbidity onset over a 27-year period in Denmark. Annual estimates of first hospitalization and the population at risk for 1987 to 2014 were identified using population-based registers. Sex-specific life tables were constructed, and the average age, the threshold age, and the coefficient of variation in age at first hospitalization were calculated. On average, first admissions lasting two or more days shifted towards older ages between 1987 and 2014. The average age at hospitalization increased from 67.8 years (95% CI 67.7-67.9) to 69.5 years (95% CI 69.4-69.6) in men, and 69.1 (95% CI 69.1-69.2) to 70.5 years (95% CI 70.4-70.6) in women. Variation in age at first admission increased slightly as the coefficient of variation increased from 9.1 (95% CI 9.0-9.1) to 9.9% (95% CI 9.8-10.0) among men, and from 10.3% (95% CI 10.2-10.4) to 10.6% (95% CI 10.5-10.6) among women. Our results suggest populations are ageing with better health today than in the past, but experience increasing diversity in healthy ageing. Pensions, social care, and health services will have to adapt to increasingly heterogeneous ageing populations, a phenomenon that average measures of morbidity do not capture.

Intravascular Cooling Device Versus Esophageal Heat Exchanger for Mild Therapeutic Hypothermia in an Experimental Setting.

BACKGROUND: Targeted temperature management is a standard therapy for unconscious survivors of cardiac arrest. To date, multiple cooling methods are available including invasive intravascular cooling devices (IVDs), which are widely used in the clinical setting. Recently, esophageal heat exchangers (EHEs) have been developed providing cooling via the esophagus that is located close to the aorta and inferior vena cava. The objective was to compare mean cooling rates, as well as differences, to target temperature during maintenance and the rewarming period of IVD and EHE. METHODS: The study was conducted in 16 female domestic pigs. After randomization to either IVD or EHE (n = 8/group), core body temperature was reduced to 33°C. After 24 hours of maintenance (33°C), animals were rewarmed using a target rate of 0.25°C/h for 10 hours. All cooling phases were steered by a closed-loop feedback system between the internal jugular vein and the chiller. After euthanasia, laryngeal and esophageal tissue was harvested for histopathological examination. RESULTS: Mean cooling rates (4.0°C/h ± 0.4°C/h for IVD and 2.4°C/h ± 0.3°C/h for EHE; P < .0008) and time to target temperature (85.1 ± 9.2 minutes for IVD and 142.0 ± 21.2 minutes for EHE; P = .0008) were different. Mean difference to target temperature during maintenance (0.07°C ± 0.05°C for IVD and 0.08°C ± 0.10°C for EHE; P = .496) and mean rewarming rates (0.2°C/h ± 0.1°C/h for IVD and 0.3°C/h ± 0.2°C/h for EHE; P = .226) were similar. Relevant laryngeal or esophageal tissue damage could not be detected. There were no significant differences in undesired side effects (eg, bradycardia or tachycardia, hypokalemia or hyperkalemia, hypoglycemia or hyperglycemia, hypotension, overcooling, or shivering). CONCLUSIONS: After insertion, target temperatures could be reached faster by IVD compared to EHE. Cooling performance of IVD and EHE did not significantly differ in maintaining target temperature during a targeted temperature management process and in active rewarming protocols according to intensive care unit guidelines in this experimental setting.

Incidence of peri-operative paediatric cardiac arrest and the influence of a specialised paediatric anaesthesia team: Retrospective cohort study.

BACKGROUND: Peri-operative critical events are still a major problem in paediatric anaesthesia care. Access to more experienced healthcare teams might reduce the adverse event rate and improve outcomes. OBJECTIVE: The current study analysed incidences of peri-operative paediatric cardiac arrest before and after implementation of a specialised paediatric anaesthesia team and training programme. DESIGN: Retrospective cohort study with before-and-after analysis. SETTING: Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Germany. PATIENTS: A total of 36 243 paediatric anaesthetics (0 to 18 years) were administered between 2008 and 2016. INTERVENTION: Implementation of a specialised paediatric anaesthesia team and training programme occurred in 2014 This included hands-on supervised training in all fields of paediatric anaesthesia, double staffing for critical paediatric cases and a 24/7 emergency team. A logistic regression analysis with risk factors (age, ASA physical status, emergency) was used to evaluate the impact of implementation of the specialised paediatric anaesthesia team. MAIN OUTCOME MEASURES: Incidences of peri-operative paediatric cardiac arrest and anaesthesia-attributable cardiac arrest before and after the intervention. RESULTS: Twelve of 25 paediatric cardiac arrests were classified as anaesthesia-attributable. The incidence of overall peri-operative paediatric cardiac arrest was 8.1/10 000 (95% CI 5.2 to 12.7) in the period 2008 to 2013 and decreased to 4.6/10 000 (95% CI 2.1 to 10.2) in 2014 to 2016. Likewise, the incidence of anaesthesia-attributable cardiac arrest was lower after 2013 [1.6/10 000 (95% CI 0.3 to 5.7) vs. 4.3/10 000 (95% CI 2.3 to 7.9)]. Using logistic regression, children anaesthetised after 2013 had nearly a 70% lower probability of anaesthesia-attributable cardiac arrest (odds ratio 0.306, 95% CI 0.067 to 1.397; P = 0.1263). For anaesthesia-attributable cardiac arrest, young age was the most contributory risk factor, whereas in overall paediatric cardiac arrest, ASA physical statuses 3 to 5 played a more important role. CONCLUSION: In this study on incidences of peri-operative paediatric cardiac arrest from a European tertiary care university hospital, implementation of a specialised paediatric anaesthesia team and training programme was associated with lower incidences of peri-operative paediatric cardiac arrest and a reduced probability of anaesthesia-attributable cardiac arrest.

Prolonged antibiotic prophylaxis after thoracoabdominal esophagectomy does not reduce the risk of pneumonia in the first 30 days: a retrospective before-and-after analysis.

PURPOSE: Thoracoabdominal esophageal resection for malignant disease is frequently associated with pulmonary infection. Whether prolonged antibiotic prophylaxis beyond a single perioperative dose is advantageous in preventing pulmonary infection after thoracoabdominal esophagectomy remains unclear. METHODS: In this retrospective before-and-after analysis, 173 patients between January 2009 and December 2014 from a prospectively maintained database were included. We evaluated the effect of a 5-day postoperative course of moxifloxacin, which is a frequently used antimicrobial agent for pneumonia, on the incidence of pulmonary infection and mortality after thoracoabdominal esophagectomy. RESULTS: 104 patients received only perioperative antimicrobial prophylaxis (control group) and 69 additionally received a 5-day postoperative antibiotic therapy with moxifloxacin (prolonged-course). 22 (12.7%) of all patients developed pneumonia within the first 30 days after surgery. No statistically significant differences were seen between the prolonged group and control group in terms of pneumonia after 7 (p = 0.169) or 30 days (p = 0.133), detected bacterial species (all p > 0.291) and 30-day mortality (5.8 vs 10.6%, p = 0.274). CONCLUSION: A preemptive 5-day postoperative course of moxifloxacin does not reduce the incidence of pulmonary infection and does not improve mortality after thoracoabdominal esophagectomy.

Incidence and risk factors of anaesthesia-related perioperative cardiac arrest: A 6-year observational study from a tertiary care university hospital.

BACKGROUND: In recent decades, the incidences of anaesthesia-related perioperative mortality and adverse outcomes have decreased drastically. However, to date, data on perioperative cardiac arrest and risk factors of perioperative cardiac arrest from European countries are scarce. OBJECTIVES: To determine the incidences of perioperative cardiac arrest and rates of anaesthesia-related and anaesthesia-contributory cardiac arrest. Identification of pre-existing risk factors leading to perioperative cardiac arrest. DESIGN: Retrospective cohort study. SETTING: Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Germany. INTERVENTIONS: Perioperative critical incident reports between 2007 and 2012 were screened, and reports on cardiac arrest within 24 h postoperatively were identified. Cardiac arrests were classified as 'anaesthesia-related', 'anaesthesia-contributory' or 'anaesthesia-unrelated' by two reviewers independently. Univariate and multi-variate logistic regression analysis was used to identify risk factors associated with perioperative cardiac arrest. RESULTS: Analysis of 318 critical incidents from 169 500 anaesthetics revealed 99 perioperative cardiac arrests. This is an overall incidence of perioperative cardiac arrest of 5.8/10 000 anaesthetics [95% confidence interval (CI), 4.7 to 7.0]. The rate of anaesthesia-related cardiac arrest was 0.7/10 000 (95% CI, 0.3 to 1.1), and the rate of anaesthesia-contributory cardiac arrest was 1.7/10 000 (95% CI, 1.1 to 2.3). Most cardiac arrests related to anaesthesia were due to respiratory events. From the multi-variate analysis, American Society of Anesthesiologists physical status grade at least 3 [P = 0.007, odds ratio (OR) 2.59 (95% CI, 1.29 to 5.19)], emergency surgery [P < 0.001, OR 4.00 (95% CI, 2.15 to 7.54)] and pre-existing cardiomyopathy [P < 0.001, OR 17.48 (95% CI, 6.18 to 51.51)] emerged as predictors of cardiac arrest. CONCLUSION: These first available European data on perioperative cardiac arrest from a large unselected cohort indicate that the overall perioperative incidence of cardiac arrest at our institution was slightly lower than published in the literature, whereas rates of anaesthesia-related and anaesthesia-contributory cardiac arrest were comparable. Most cardiac arrests related to anaesthesia were due to respiratory events. American Society of Anesthesiologists physical status grade at least 3, emergency surgery and pre-existing cardiomyopathy appear to be relevant risk factors for cardiac arrest.

Self-confidence and level of knowledge after cardiopulmonary resuscitation training in 14 to 18-year-old schoolchildren: A randomised-interventional controlled study in secondary schools in Germany.

BACKGROUND: Education of schoolchildren in cardiopulmonary resuscitation (CPR) is a strategic goal for improvement of bystander CPR in society. OBJECTIVE(S): The primary objective was to analyse the impact of CPR training on the resuscitation knowledge and self-confidence of secondary schoolchildren. In addition, independent predictors of improved CPR knowledge and self-confidence were investigated. DESIGN: Randomised-interventional controlled study. SETTING: Four secondary schools in Germany. PARTICIPANTS: Four hundred and twenty-four schoolchildren aged from 14 to 18 years were included into the study. Fifty-one percent were female, and 33% had an immigrant background. INTERVENTION: The intervention group received a 90-min CPR training session, whereas controls had no intervention. Levels of knowledge and self-confidence in initiating CPR were analysed by a study questionnaire before (t0), 90 min after (t1) and 6 months after training (t2). MAIN OUTCOME MEASURES: Based on the evaluation of study questionnaires, the primary endpoint was to determine the development of resuscitation knowledge and self-confidence in initiating cardiopulmonary resuscitation at survey time-points t0, t1 and t2. RESULTS: Schoolchildren in the intervention group (n=207) showed a significantly higher level of knowledge (P < 0.001) and self-confidence (P < 0.001) at t1 and t2 compared with controls (n=217). Age was a predictor for long-term self-confidence [odds ratio (OR), 1.20; 95% confidence interval (95% CI), 1.02 to 1.41; P = 0.032]. The long-term benefit in the level of knowledge and self-confidence were significantly higher in native compared with immigrant schoolchildren: (OR, 1.79; 95% CI, 1.14 to 2.82; P = 0.011) and (OR, 1.67; 95% CI, 1.07 to 2.60; P = 0.024), respectively. CONCLUSION: Guideline compliant (90 min) theoretical and practical CPR training improves the level of knowledge and self-confidence in 14 to 18-year-old schoolchildren. Older schoolchildren are more likely to have increased self-confidence with respect to initiating CPR. Schoolchildren with an immigrant background showed a significantly lower increase in their level of knowledge and self-confidence compared with native children. Adaptation and simplification of teaching materials and further research on educational methods for CPR are urgently needed to enable a sustainable approach to teaching CPR, which also produces a long-lasting effect in the entire population.

Time Dependent Pathway Activation of Signalling Cascades in Rat Organs after Short-Term Hyperoxia.

Administration of oxygen is one of the most common interventions in medicine. Previous research showed that differential regulated proteins could be linked to hyperoxia-associated signaling cascades in different tissues. However, it still remains unclear which signaling pathways are activated by hyperoxia. The present study analyses hyperoxia-induced protein alterations in lung, brain, and kidney tissue using a proteomic and bioinformatic approach. Pooled data of 36 Wistar rats exposed to hyperoxia were used. To identify possible hyperoxia biomarkers, and to evaluate the relationship between protein alterations in hyperoxia affected organs and blood, proteomics data from brain, lung, and kidney were analyzed. Functional network analyses (IPA®, PathwaysStudio®, and GENEmania®) in combination with hierarchical cluster analysis (Perseus®) was used to identify relevant pathways and key proteins. Data of 54 2D-gels with more than 2500 significantly regulated spots per gel were collected. Thirty-eight differentially expressed proteins were identified and consecutively analyzed by bioinformatic methods. Most differences between hyperoxia and normoxia (21 proteins up-regulated, 17 proteins down-regulated) were found immediately after hyperoxia (15 protein spots), followed by day 3 (13 spots), and day 7 (10 spots). A highly significant association with inflammation and the inflammatory response was found. Cell proliferation, oxidative stress, apoptosis and cell death as well as cellular functions were revealed to be affected. Three hours of hyperoxia resulted in significant alterations of protein expression in different organs (brain, lung, kidney) up to seven days after exposure. Further studies are required to interpret the relevance of protein alterations in signaling cascades during/after hyperoxia.

Procalcitonin-guided antibiotic treatment in critically ill patients.

PURPOSE: In critically ill patients, length of antibiotic treatment can be effectively guided by procalcitonin (PCT) protocols. International sepsis guidelines and guidelines on antibiotic stewardship strategies recommend PCT as helpful laboratory marker for a rational use of antibiotics. A number of studies and meta-analyses have confirmed the effectiveness of PCT-protocols for shortening antibiotic treatment without compromising clinical outcome in critically ill patients. But in clinical practice, there is still uncertainty how to interpret PCT levels and how to adjust antibiotic treatment in various infectious situations, especially in the perioperative period. METHODS: This narrative review gives an overview on the application of PCT-protocols in critically ill patients with severe bacterial infections on the basis of 5 case reports and the available literature. Beside strengths and limitations of this biomarker, also varying kinetics and different maximum values with regard to the infectious focus and pathogens are discussed. RESULTS: PCT-guided antibiotic treatment appears to be safe and effective. Most of the studies revealed a shorter antibiotic treatment without negative clinical outcomes. Cost effectiveness is still a matter of debate and effects on bacterial resistance due to shorter treatments, possible lower rates of drug-related adverse events, or decreased rates of Clostridium difficile infections are not yet evaluated. CONCLUSION: Guidance of antibiotic treatment can effectively be supported by PCT-protocols. However, it is important to consider the limitations of this biomarker and to use PCT protocols along with antibiotic stewardship programmes and regular clinical rounds together with infectious diseases specialists.

Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum.

Hypobaric hypoxia (HH) during airline travel induces several (patho-) physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min) in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE) and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF). Biological functions of regulated proteins were identified using functional network analysis (GeneMania®, STRING®, and Perseus® software). In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU) was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades "regulation of haemostasis" (four proteins), "metabolism" (five proteins), and "leukocyte mediated immune response" (five proteins). Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight), analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis.

Airway management for anaesthesia in the ambulatory setting.

PURPOSE OF REVIEW: The number of anaesthetic procedures in the ambulatory setting is steadily increasing. During the last years, more and more patients with complex medical conditions undergo ambulatory interventions. This review will focus on airway management practices, but especially on techniques used in the ambulatory setting. It will highlight recent literature published in the focus of ambulatory anaesthesia and will discuss relevant findings of the last year. METHODS: Literature search and analysis performed independently by two reviewers. RECENT FINDINGS: Practical points to improve success of anaesthesia and to avoid complications in the ambulatory setting are provided. In addition to concepts for the (un)expected difficult airway, new supraglottic devices, and modern concepts for teleconsultation, are discussed. SUMMARY: There are several points which should be considered for ambulatory anaesthesia. Selected patient groups (e.g., obstructive sleep apnoea, obesity) may have a higher anaesthesia-related risk. To handle the more and more complex conditions in a growing number of ambulatory patients, straightforward concepts, especially for the (un)expected difficult airway, are required.

Estimating quality-adjusted life expectancy (QALE) for local authorities in Great Britain and its association with indicators of the inclusive economy: a cross-sectional study.

OBJECTIVES: Quantifying area-level inequalities in population health can help to inform policy responses. We describe an approach for estimating quality-adjusted life expectancy (QALE), a comprehensive health expectancy measure, for local authorities (LAs) in Great Britain (GB). To identify potential factors accounting for LA-level QALE inequalities, we examined the association between inclusive economy indicators and QALE. SETTING: 361/363 LAs in GB (lower tier/district level) within the period 2018-2020. DATA AND METHODS: We estimated life tables for LAs using official statistics and utility scores from an area-level linkage of the Understanding Society survey. Using the Sullivan method, we estimated QALE at birth in years with corresponding 80% CIs. To examine the association between inclusive economy indicators and QALE, we used an open access data set operationalising the inclusive economy, created by the System Science in Public Health and Health Economics Research consortium. RESULTS: Population-weighted QALE estimates across LAs in GB were lowest in Scotland (females/males: 65.1 years/64.9 years) and Wales (65.0 years/65.2 years), while they were highest in England (67.5 years/67.6 years). The range across LAs for females was from 56.3 years (80% CI 45.6 to 67.1) in Mansfield to 77.7 years (80% CI 65.11 to 90.2) in Runnymede. QALE for males ranged from 57.5 years (80% CI 40.2 to 74.7) in Merthyr Tydfil to 77.2 years (80% CI 65.4 to 89.1) in Runnymede. Indicators of the inclusive economy accounted for more than half of the variation in QALE at the LA level (adjusted R2 females/males: 50%/57%). Although more inclusivity was generally associated with higher levels of QALE at the LA level, this association was not consistent across all 13 inclusive economy indicators. CONCLUSIONS: QALE can be estimated for LAs in GB, enabling further research into area-level health inequalities. The associations we identified between inclusive economy indicators and QALE highlight potential policy priorities for improving population health and reducing health inequalities.

Procalcitonin-guided algorithm to reduce length of antibiotic therapy in patients with severe sepsis and septic shock.

BACKGROUND: Procalcitonin (PCT)-protocols to guide antibiotic treatment in severe infections are known to be effective. But less is known about the long-term effects of such protocols on antibiotic consumption under real life conditions. This retrospective study analyses the effects on antibiotic use in patients with severe sepsis and septic shock after implementation of a PCT-protocol. METHODS: We conducted a retrospective ICU-database search for adult patients between 2005 and 2009 with sepsis and organ dysfunction who where treated accordingly to a PCT-guided algorithm as follows: Daily measurements of PCT (BRAHMS PCT LIA(®); BRAHMS Aktiengesellschaft, Hennigsdorf, Germany). Antibiotic therapy was discontinued if 1) clinical signs and symptoms of infection improved and PCT decreased to ≤1 ng/ml, or 2) if the PCT value was >1 ng/ml, but had dropped to 25-35% of the initial value within three days. The primary outcome parameters were: antibiotic days on ICU, ICU re-infection rate, 28-day mortality rate, length of stay (LOS) in ICU, mean antibiotic costs (per patient) and ventilation hours. Data from 141 patients were included in our study. Primary outcome parameters were analysed using covariance analyses (ANCOVA) to control for effects by gender, age, SAPS II, APACHE II and effective cost weight. RESULTS: From baseline data of 2005, duration of antibiotic therapy was reduced by an average of 1.0 day per year from 14.3 ±1.2 to 9.0 ±1.7 days in 2009 (p=0.02). ICU re-infection rate was decreased by yearly 35.1% (95% CI -53 to -8.5; p=0.014) just as ventilation hours by 42 hours per year (95% CI -72.6 to -11.4; p=0.008). ICU-LOS was reduced by 2.7 days per year (p<0.001). Trends towards an average yearly reduction of 28-day mortality by -22.4% (95% CI -44.3 to 8.1; p=0.133) and mean cost for antibiotic therapy/ patient by -14.3 Euro (95% CI -55.7 to 27.1) did not reach statistical significance. CONCLUSIONS: In a real-life clinical setting, implementation of a PCT-protocol was associated with a reduced duration of antibiotic therapy in septic ICU patients without compromising clinical or economical outcomes. GERMAN CLINICAL TRIALS REGISTER: DRKS00003490.

Systems science methods in public health: what can they contribute to our understanding of and response to the cost-of-living crisis?

BACKGROUND: Many complex public health evidence gaps cannot be fully resolved using only conventional public health methods. We aim to familiarise public health researchers with selected systems science methods that may contribute to a better understanding of complex phenomena and lead to more impactful interventions. As a case study, we choose the current cost-of-living crisis, which affects disposable income as a key structural determinant of health. METHODS: We first outline the potential role of systems science methods for public health research more generally, then provide an overview of the complexity of the cost-of-living crisis as a specific case study. We propose how four systems science methods (soft systems, microsimulation, agent-based and system dynamics models) could be applied to provide more in-depth understanding. For each method, we illustrate its unique knowledge contributions, and set out one or more options for studies that could help inform policy and practice responses. RESULTS: Due to its fundamental impact on the determinants of health, while limiting resources for population-level interventions, the cost-of-living crisis presents a complex public health challenge. When confronted with complexity, non-linearity, feedback loops and adaptation processes, systems methods allow a deeper understanding and forecasting of the interactions and spill-over effects common with real-world interventions and policies. CONCLUSIONS: Systems science methods provide a rich methodological toolbox that complements our traditional public health methods. This toolbox may be particularly useful in early stages of the current cost-of-living crisis: for understanding the situation, developing solutions and sandboxing potential responses to improve population health.

Impact of the COVID-19 pandemic on emergency medical resources : An observational multicenter study including all hospitals in a major urban center of the Rhein-Ruhr metropolitan region.

BACKGROUND: With the coronavirus disease 2019 (COVID-19) outbreak hospitals prepared for increasing numbers of patients without knowing how patient populations were evolving and what resources would be required. The present study aimed to analyze the impact of the local COVID-19 pandemic on emergency resources of all hospitals in a major urban center (Mönchengladbach) in Germany. METHODS: This observational multicenter study involved all acute care hospitals (n = 4). Systemic emergency department (ED) parameters from weeks 4-24 in 2020 were compared to the corresponding period in 2019 for each hospital and in a summative data analysis using a logistic regression model. RESULTS: The first regional COVID-19 patients were detected in week 9 of 2020. The cumulative number of ED visits dropped from 34,659 in 2019 to 28,008 in 2020. Weekly ED visits per hospital decreased from week 8 onwards between 38% and 48% per week and hospital and began to rise again after week 16. The pooled data analysis of ED patients showed significant decreases in outpatient visits (20,152 vs. 16,477, p < 0.001), hospital admissions (14,507 vs. 11,531, p < 0.001), and work-related accidents (2290 vs. 1468, p < 0.001). The decrease in ED to ICU admissions showed no significance (2093 vs. 1566, p = 0.255). The decline in ED cases was equally distributed between the medical specialties. CONCLUSION: The regional COVID-19 outbreak led to significantly reduced ED contacts in a German major urban region after the first COVID-19 cases appeared. Both hospital admissions and the number of ED to ICU admissions decreased, whereas the ratio of emergency outpatients vs. inpatients remained stable. Therefore, it can be assumed that patients with severe medical problems did not seek emergency care. These secondary effects of the pandemic on healthcare and the socioeconomic impact should be analyzed further.

Large socioeconomic gap in period life expectancy and life years spent with complications of diabetes in the Scottish population with type 1 diabetes, 2013-2018.

BACKGROUND: We report the first study to estimate the socioeconomic gap in period life expectancy (LE) and life years spent with and without complications in a national cohort of individuals with type 1 diabetes. METHODS: This retrospective cohort study used linked healthcare records from SCI-Diabetes, the population-based diabetes register of Scotland. We studied all individuals aged 50 and older with a diagnosis of type 1 diabetes who were alive and residing in Scotland on 1 January 2013 (N = 8591). We used the Scottish Index of Multiple Deprivation (SIMD) 2016 as an area-based measure of socioeconomic deprivation. For each individual, we constructed a history of transitions by capturing whether individuals developed retinopathy/maculopathy, cardiovascular disease, chronic kidney disease, and diabetic foot, or died throughout the study period, which lasted until 31 December 2018. Using parametric multistate survival models, we estimated total and state-specific LE at an attained age of 50. RESULTS: At age 50, remaining LE was 22.2 years (95% confidence interval (95% CI): 21.6 - 22.8) for males and 25.1 years (95% CI: 24.4 - 25.9) for females. Remaining LE at age 50 was around 8 years lower among the most deprived SIMD quintile when compared with the least deprived SIMD quintile: 18.7 years (95% CI: 17.5 - 19.9) vs. 26.3 years (95% CI: 24.5 - 28.1) among males, and 21.2 years (95% CI: 19.7 - 22.7) vs. 29.3 years (95% CI: 27.5 - 31.1) among females. The gap in life years spent without complications was around 5 years between the most and the least deprived SIMD quintile: 4.9 years (95% CI: 3.6 - 6.1) vs. 9.3 years (95% CI: 7.5 - 11.1) among males, and 5.3 years (95% CI: 3.7 - 6.9) vs. 10.3 years (95% CI: 8.3 - 12.3) among females. SIMD differences in transition rates decreased marginally when controlling for time-updated information on risk factors such as HbA1c, blood pressure, BMI, or smoking. CONCLUSIONS: In addition to societal interventions, tailored support to reduce the impact of diabetes is needed for individuals from low socioeconomic backgrounds, including access to innovations in management of diabetes and the prevention of complications.