Understanding the biases to sepsis surveillance and quality assurance caused by inaccurate coding in administrative health data.

PURPOSE: Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care. METHODS: We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015-2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information. RESULTS: ICD-coding of sepsis in IAHD showed high positive predictive value (76.9-85.7% depending on sepsis definition), but low sensitivity (26.8-38%), which led to an underestimation of sepsis incidence (1.4% vs. 3.3% for severe sepsis-1). Not naming sepsis in the chart was strongly associated with under-coding of sepsis. The frequency of correctly naming sepsis and ICD-coding of sepsis varied strongly between hospitals (range of sensitivity of naming: 29-71.7%, of ICD-diagnosis: 10.7-58.5%). Risk-adjusted mortality of sepsis per hospital calculated from coding in IAHD showed no substantial correlation to reference standard risk-adjusted mortality (r = 0.09). CONCLUSION: Due to the under-coding of sepsis in IAHD, previous epidemiological studies underestimated the burden of sepsis in Germany. There is a large variability between hospitals in accuracy of diagnosing and coding of sepsis. Therefore, IAHD alone is not suited to assess quality of sepsis care.

Comparison of post-COVID-19 symptoms in patients infected with the SARS-CoV-2 variants delta and omicron-results of the Cross-Sectoral Platform of the German National Pandemic Cohort Network (NAPKON-SUEP).

PURPOSE: The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. METHODS: We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. RESULTS: We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI 0.73-0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. CONCLUSION: With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. CLINICAL TRAIL REGISTRATION: The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).

Use of cell salvage in obstetrics in Germany: analysis of national database of 305 610 cases with peripartum haemorrhage.

BACKGROUND: One of the leading causes of maternal death worldwide is severe obstetric haemorrhage after childbirth. Use of intraoperative cell salvage is strongly recommended by international guidelines on patient blood management. Recent data provide strong evidence that use of cell salvage in obstetrics is effective and safe in women with postpartum haemorrhage resulting in fewer transfusion-related adverse events and shorter hospital stay. We retrospectively analysed the use of cell salvage in bleeding women during delivery for a period of 10 yr in German hospitals. METHODS: Data from the German Federal Statistical Office were used that covers all in-hospital birth deliveries from 2011 to 2020. Prevalence of peripartum haemorrhage (pre-, intra-, and post-partum haemorrhage), comorbidities, peripartum complications, administration of blood products, and use of cell salvage were analysed. RESULTS: Of 6 356 046 deliveries in Germany, 305 610 women (4.8%) suffered from peripartum haemorrhage. Of all women with peripartum haemorrhage, postpartum haemorrhage was the main cause for major obstetric haemorrhage (92.33%). Cell salvage was used in only 228 (0.07%) of all women with peripartum haemorrhage (cell salvage group). In women undergoing Caesarean delivery with postpartum haemorrhage, cell salvage was used in only 216 out of 70 450 women (0.31%). CONCLUSION: Cell salvage during peripartum haemorrhage is rarely used in Germany. There is tremendous potential for the increased use of cell salvage in peripartum haemorrhage nationwide.

Effect of using smaller blood volume tubes and closed blood collection devices on total blood loss in patients undergoing major cardiac and vascular surgery.

BACKGROUND: Diagnostic laboratory tests are an integral part of managing hospitalized patients. In particular, patients in the intensive care units (ICUs) can experience a concerning amount of blood loss due to diagnostic testing, which can increase the risk developing iatrogenic anemia. Several interventions exist to curtail avoidable blood loss, for example computerized decision support, smaller phlebotomy tubes, and other blood conservation devices. Nevertheless, use of these interventions is not standardized. Therefore, the objective of our study was to quantify the daily phlebotomy volume taken from patients who had undergone major cardiac or vascular surgery. METHODS: We estimated the number of blood analyses and volumes of drawn blood of 400 consecutive patients (≥ 18 yr) undergoing major cardiac or vascular surgery. The amount of blood saved using small-volume tubes and in combination with blood conservation device rather than standard-volume tubes was estimated for serum chemistry (serum), ethylenediaminetetraacetic acid (EDTA) tubes, sodium citrate coagulation (SCC) tubes, and arterial blood gas (ABG) analysis. RESULTS: The mean total blood loss due to phlebotomy drawing using standard-volume tubes during hospitalization was 167.9 mL (95% confidence interval [CI], 158.0 to 177.8), 255.6 mL (95% CI, 226.5 to 284.6), and 695.3 mL (95% CI, 544.1 to 846.4) for patients undergoing cardiac surgery with a hospital length of stay (LOS) of 0-10, 11-20, and ≥ 21 days, respectively. The mean total blood loss due to phlebotomy during hospitalization was 80.5 mL (95% CI, 70.5 to 90.6), 225.0 mL (95% CI, 135.1 to 314.8 mL) and 470.3 mL (95% CI, 333.5 to 607.1) for vascular surgery patients with LOS 0-10, 11-20, and ≥ 21 days, respectively. Patients with at least a two-day stay at the ICU had a mean blood loss of 146.6 mL (95% CI, 134.6 to 158.6 mL) and those with ≥ 11 days incurred a loss of 1,428 mL (95% CI, 1,117.8 to 1,739.2). The use of closed blood collection device and small-volume tubes (serum, EDTA, SCC, and ABG) reduced blood loss by 82.8 mL for patients with an ICU stay of 2 days and up to 824.0 mL for patients with a ICU stay of ≥ 11 days. CONCLUSION: Diagnostic laboratory tests are associated with significant patient blood loss, but are a modifiable risk factor. The use of small-volume tubes and closed blood collection devices decreases the volume of patient blood drawn for analysis and prevents blood waste.

RéSUMé: CONTEXTE: Les tests diagnostiques de laboratoire font partie intégrante de la prise en charge des personnes hospitalisées. Plus spécifiquement, la patientèle des unités de soins intensifs (USI) peut perdre une quantité inquiétante de sang en raison des tests de diagnostic, ce qui peut augmenter le risque d'anémie iatrogène. Plusieurs interventions existent pour réduire les pertes de sang évitables, par exemple une aide à la décision informatisée, des tubes de phlébotomie plus petits et d'autres dispositifs de conservation du sang. Néanmoins, le recours à ces interventions n'est pas normalisé. Par conséquent, l'objectif de notre étude était de quantifier le volume quotidien de phlébotomie prélevée chez des patient·es ayant bénéficié d'une chirurgie cardiaque ou vasculaire majeure. MéTHODE: Nous avons estimé le nombre d'analyses sanguines et les volumes de sang prélevés de 400 personnes consécutives (≥ 18 ans) bénéficiant d'une chirurgie cardiaque ou vasculaire majeure. La quantité de sang économisée à l'aide de tubes de petit volume et en combinaison avec un dispositif de conservation du sang plutôt que des tubes de volume standard a été estimée pour la chimie sérique (sérum), les tubes d'acide éthylène-diamine-tétra-acétique (EDTA), les tubes de coagulation au citrate de sodium (CCS) et l'analyse des gaz du sang artériel (GSA). RéSULTATS: La perte sanguine totale moyenne due au prélèvement de phlébotomie à l'aide de tubes de volume standard pendant l'hospitalisation était de 167,9 mL (intervalle de confiance [IC] à 95 %, 158,0 à 177,8), 255,6 mL (IC 95 %, 226,5 à 284,6) et 695,3 mL (IC 95 %, 544,1 à 846,4) chez les patient·es bénéficiant d'une chirurgie cardiaque avec une durée de séjour à l'hôpital de 0 à 10, 11 à 20, et ≥ 21 jours, respectivement. La perte sanguine totale moyenne due à la phlébotomie pendant l'hospitalisation était de 80,5 mL (IC 95 %, 70,5 à 90,6), 225,0 mL (IC 95 %, 135,1 à 314,8 mL) et 470,3 mL (IC 95 %, 333,5 à 607,1) chez les patient·es ayant bénéficié d'une chirurgie vasculaire avec des durées de séjour de 0-10, 11-20 et ≥ 21 jours, respectivement. Les patient·es ayant séjourné au moins deux jours à l'USI ont eu une perte de sang moyenne de 146,6 mL (IC 95 %, 134,6 à 158,6 mL) et celles et ceux ayant séjourné ≥ 11 jours ont subi une perte de 1428 mL (IC 95 %, 1117,8 à 1739,2). L'utilisation d'un dispositif de prélèvement sanguin fermé et de tubes de petit volume (sérum, EDTA, SCC et gsa) a réduit la perte de sang de 82,8 mL pour les patient·es ayant séjourné à l'USI 2 jours et jusqu'à 824,0 mL pour les patient·es ayant séjourné en USI ≥ 11 jours. CONCLUSION: Les tests de laboratoire diagnostiques sont associés à une perte de sang importante chez les patient·es, mais constituent un facteur de risque modifiable. L'utilisation de tubes de petit volume et de dispositifs fermés de prélèvement sanguin diminue le volume de sang prélevé pour analyse et prévient le gaspillage de sang.

Decoding the meaning of medical guidelines and their medicolegal implications.

Medical practice guidelines (MPGs) are important in medicine to ensure well tolerated and effective healthcare. They provide evidence-based recommendations for healthcare professionals in daily clinical settings. MPGs help patients and practitioners make informed decisions, ensure quality of care, allocate healthcare resources effectively and reduce legal liability. MPGs have medicolegal implications, as they influence clinical decision-making and patient outcomes, which can impact liability and malpractice cases. They define the standard of care within the healthcare industry and provide best practice recommendations. MPGs are a cornerstone of the informed consent process, as they facilitate a shared decision support system and they provide valuable evidence-based recommendations on various treatments or medical options. Finally, MPGs are also relevant in medical claims; thus, adherence to MPGs is highly encouraged in order to assure the best medical care. Nonetheless, MPGs have limitations and we advocate for wise usage of MPGs combined with the expertise of trained physicians that allows for individualisation and evidence-based recommendations. In this review, we describe the potential legal implications that MPGs may represent for healthcare providers and the role that MPGs have in daily practice at different stages in the doctor--patient relationship.

Current concepts in the use of cell salvage in obstetrics.

PURPOSE OF REVIEW: The worldwide leading cause of maternal death is severe maternal hemorrhage. Maternal hemorrhage can be profound leading to an entire loss of blood volume. In the past two decades, Patient Blood Management has evolved to improve patient's care and safety. In surgeries with increased blood loss exceeding 500 ml, the use of cell salvage is strongly recommended in order to preserve the patient's own blood volume and to minimize the need for allogeneic red blood cell (RBC) transfusion. In this review, recent evidence and controversies of the use of cell salvage in obstetrics are discussed. RECENT FINDINGS: Numerous medical societies as well as national and international guidelines recommend the use of cell salvage during maternal hemorrhage. SUMMARY: Intraoperative cell salvage is a strategy to maintain the patient's own blood volume and decrease the need for allogeneic RBC transfusion. Historically, cell salvage has been avoided in the obstetric population due to concerns of iatrogenic amniotic fluid embolism (AFE) or induction of maternal alloimmunization. However, no definite case of AFE has been reported so far. Cell salvage is strongly recommended and cost-effective in patients with predictably high rates of blood loss and RBC transfusion, such as women with placenta accreta spectrum disorder. However, in order to ensure sufficient practical experience in a multiprofessional obstetric setting, liberal use of cell salvage appears advisable.

Current concepts in postpartum anemia management.

PURPOSE OF REVIEW: Postpartum anemia (PPA) is common in women after childbirth and affects about 50-80% of all women worldwide. Iron deficiency (ID) is the main cause for anemia and constitutes a potentially preventable condition with great impact on the mother's physical and mental condition after delivery. In most cases, PPA is associated with antenatal ID and peripartum blood losses. Numerous published studies confirmed the positive effect of PPA diagnosis and treatment. RECENT FINDINGS: Iron deficiency as well as iron deficiency anemia (IDA) are common in the postpartum period and represent significant health problems in women of reproductive age. SUMMARY: Important movements towards early detection and therapy of postpartum anemia have been observed. However, postpartum anemia management is not implemented on a large scale as many healthcare professionals are not aware of the most recent findings in the field. Diagnosis and therapy of PPA, particularly iron supplementation in ID and IDA, has proven to be highly effective with a tremendous effect on women's wellbeing and outcome.

[Relevance of the Allen Test before Catheterization of the Radial Artery]. / Wie relevant ist der Allen-Test vor Kanülierung der A. radialis?

Arterial catheterization is considered to be standard procedure for patients undergoing general anesthesia. The most common puncture site is the radial artery (RA), which carries a risk of RA occlusion. Several pieces of literature still recommend the performance of the Allen test (AT) to assess the circulation of the palmar arch. However, the result of the AT differs largely depending on the examiner and the test is not able to predict ischemic events correctly. Thus it appears that the performance of an AT is not mandatory before arterial cannulation.

The protective effect of low-dose minocycline on brain microvascular ultrastructure in a rodent model of subarachnoid hemorrhage.

The multifaceted nature of subarachnoid hemorrhage (SAH) pathogenesis is poorly understood. To date, no pharmacological agent has been found to be efficacious for the prevention of brain injury when used for acute SAH intervention. This study was undertaken to evaluate the beneficial effects of low-dose neuroprotective agent minocycline on brain microvascular ultrastructures that have not been studied in detail. We studied SAH brain injury using an in vivo prechiasmatic subarachnoid hemorrhage rodent model. We analyzed the qualitative and quantitative ultrastructural morphology of capillaries and surrounding neuropil in the rodent brains with SAH and/or minocycline administration. Here, we report that low-dose minocycline (1 mg/kg) displayed protective effects on capillaries and surrounding cells from significant SAH-induced changes. Ultrastructural morphology analysis revealed also that minocycline stopped endothelial cells from abnormal production of vacuoles and vesicles that compromise blood-brain barrier (BBB) transcellular transport. The reported ultrastructural abnormalities as well as neuroprotective effects of minocycline during SAH were not directly mediated by inhibition of MMP-2, MMP-9, or EMMPRIN. However, SAH brain tissue treated with minocycline was protected from development of other morphological features associated with oxidative stress and the presence of immune cells in the perivascular space. These data advance the knowledge on the effect of SAH on brain tissue ultrastructure in an SAH rodent model and the neuroprotective effect of minocycline when administered in low doses.

The impact of higher protein dosing on outcomes in critically ill patients with acute kidney injury: a post hoc analysis of the EFFORT protein trial.

BACKGROUND: Based on low-quality evidence, current nutrition guidelines recommend the delivery of high-dose protein in critically ill patients. The EFFORT Protein trial showed that higher protein dose is not associated with improved outcomes, whereas the effects in critically ill patients who developed acute kidney injury (AKI) need further evaluation. The overall aim is to evaluate the effects of high-dose protein in critically ill patients who developed different stages of AKI. METHODS: In this post hoc analysis of the EFFORT Protein trial, we investigated the effect of high versus usual protein dose (≥ 2.2 vs. ≤ 1.2 g/kg body weight/day) on time-to-discharge alive from the hospital (TTDA) and 60-day mortality and in different subgroups in critically ill patients with AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria within 7 days of ICU admission. The associations of protein dose with incidence and duration of kidney replacement therapy (KRT) were also investigated. RESULTS: Of the 1329 randomized patients, 312 developed AKI and were included in this analysis (163 in the high and 149 in the usual protein dose group). High protein was associated with a slower time-to-discharge alive from the hospital (TTDA) (hazard ratio 0.5, 95% CI 0.4-0.8) and higher 60-day mortality (relative risk 1.4 (95% CI 1.1-1.8). Effect modification was not statistically significant for any subgroup, and no subgroups suggested a beneficial effect of higher protein, although the harmful effect of higher protein target appeared to disappear in patients who received kidney replacement therapy (KRT). Protein dose was not significantly associated with the incidence of AKI and KRT or duration of KRT. CONCLUSIONS: In critically ill patients with AKI, high protein may be associated with worse outcomes in all AKI stages. Recommendation of higher protein dosing in AKI patients should be carefully re-evaluated to avoid potential harmful effects especially in patients who were not treated with KRT. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT03160547) on May 17th 2017.

Penny-wise and pound-foolish: the challenges of preoperative anaemia management.

The timely correction of anaemia before major surgery is important for optimising perioperative patient outcomes. However, multiple barriers have precluded the global expansion of preoperative anaemia treatment programmes, including misconceptions about the true cost/benefit ratio for patient care and health system economics. Institutional investment and buy-in from stakeholders could lead to significant cost savings through avoided complications of anaemia and red blood cell transfusions, and through containment of direct and variable costs of blood bank laboratories. In some health systems, billing for iron infusions could generate revenue and promote growth of treatment programmes. The aim of this work is to galvanise integrated health systems worldwide to diagnose and treat anaemia before major surgery.

German Patient Blood Management Network: effectiveness and safety analysis in 1.2 million patients.

BACKGROUND: Patient Blood Management (PBM) is a patient-centred, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood whilst promoting patient safety and empowerment. The effectiveness and safety of PBM over a longer period have not yet been investigated. METHODS: We performed a prospectively designed, multicentre follow-up study with non-inferiority design. Data were retrospectively extracted case-based from electronic hospital information systems. All in-hospital patients (≥18 yr) undergoing surgery and discharged between January 1, 2010 and December 31, 2019 were included in the analysis. The PBM programme focused on three domains: preoperative optimisation of haemoglobin concentrations, blood-sparing techniques, and guideline adherence/standardisation of allogeneic blood product transfusions. The outcomes were utilisation of blood products, composite endpoint of in-hospital mortality and postoperative complications (myocardial infarction/ischaemic stroke/acute renal failure with renal replacement therapy/sepsis/pneumonia), anaemia rate at admission and discharge, and hospital length of stay. RESULTS: A total of 1 201 817 (pre-PBM: n=441 082 vs PBM: n=760 735) patients from 14 (five university/nine non-university) hospitals were analysed. Implementation of PBM resulted in a substantial reduction of red blood cell utilisation. The mean number of red blood cell units transfused per 1000 patients was 547 in the PBM cohort vs 635 in the pre-PBM cohort (relative reduction of 13.9%). The red blood cell transfusion rate was significantly lower (P<0.001) with odds ratio 0.86 (0.85-0.87). The composite endpoint was 5.8% in the PBM vs 5.6% in the pre-PBM cohort. The non-inferiority aim (safety of PBM) was achieved (P<0.001). CONCLUSIONS: Analysis of >1 million surgical patients showed that the non-inferiority condition (safety of Patient Blood Management) was fulfilled, and PBM was superior with respect to red blood cell transfusion. CLINICAL TRIAL REGISTRATION: NCT02147795.

Nirmatrelvir combined with ritonavir for preventing and treating COVID-19.

BACKGROUND: Oral nirmatrelvir/ritonavir (Paxlovid) aims to avoid severe COVID-19 in asymptomatic people or those with mild symptoms, thereby decreasing hospitalization and death. It remains to be evaluated for which indications and patient populations the drug is suitable. OBJECTIVES: To assess the efficacy and safety of nirmatrelvir/ritonavir plus standard of care (SoC) compared to SoC with or without placebo, or any other intervention for treating COVID-19 or preventing SARS-CoV-2 infection. To explore equity aspects in subgroup analyses. To keep up to date with the evolving evidence base using a living systematic review (LSR) approach and make new relevant studies available to readers in-between publication of review updates. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, Scopus, and World Health Organization COVID-19 Research Database, identifying completed and ongoing studies without language restrictions and incorporating studies up to 15 May 2023. This is a LSR. We conduct update searches every two months and make them publicly available on the open science framework (OSF) platform. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing nirmatrelvir/ritonavir plus SoC to SoC with or without placebo, or any other intervention for treatment of people with confirmed COVID-19 diagnosis, irrespective of disease severity or treatment setting, and for prevention of SARS-CoV-2 infection. We screened all studies for research integrity. Studies were ineligible if they had been retracted, or if they were not prospectively registered including appropriate ethics approval. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology and used the Cochrane RoB 2 tool. We rated the certainty of evidence using the GRADE approach for the following outcomes: 1. to treat outpatients with mild COVID-19; 2. to treat inpatients with moderate to severe COVID-19: mortality, clinical worsening or improvement, quality of life, (serious) adverse events, and viral clearance; 3. to prevent SARS-CoV-2 infection in postexposure prophylaxis (PEP); and 4. pre-exposure prophylaxis (PrEP) scenarios: SARS-CoV-2 infection, development of COVID-19 symptoms, mortality, admission to hospital, quality of life, and (serious) adverse events. We explored inequity by subgroup analysis for elderly people, socially-disadvantaged people with comorbidities, populations from low-income countries and low- to middle-income countries, and people from different ethnic and racial backgrounds. MAIN RESULTS: As of 15 May 2023, we included two RCTs with 2510 participants with mild and mild to moderate symptomatic COVID-19 in outpatient and inpatient settings comparing nirmatrelvir/ritonavir plus SoC to SoC with or without placebo. All trial participants were without previous confirmed SARS-CoV-2 infection and at high risk for progression to severe disease. Randomization coincided with the Delta wave for outpatients and Omicron wave for inpatients. Outpatient trial participants and 73% of inpatients were unvaccinated. Symptom onset in outpatients was no more than five days before randomisation and prior or concomitant therapies including medications highly dependent on CYP3A4 were not allowed. We excluded two studies due to concerns with research integrity. We identified 13 ongoing studies. Three studies are currently awaiting classification. Nirmatrelvir/ritonavir for treating people with asymptomatic or mild COVID-19 in outpatient settings Nirmatrelvir/ritonavir plus SoC compared to SoC plus placebo may reduce all-cause mortality at 28 days (risk ratio (RR) 0.04, 95% confidence interval (CI) 0.00 to 0.68; 1 study, 2224 participants; low-certainty evidence) and admission to hospital or death within 28 days (RR 0.13, 95% CI 0.07 to 0.27; 1 study, 2224 participants; low-certainty evidence). Nirmatrelvir/ritonavir plus SoC may reduce serious adverse events during the study period compared to SoC plus placebo (RR 0.24, 95% CI 0.15 to 0.41; 1 study, 2224 participants; low-certainty evidence). Nirmatrelvir/ritonavir plus SoC probably has little or no effect on treatment-emergent adverse events (RR 0.95, 95% CI 0.82 to 1.10; 1 study, 2224 participants; moderate-certainty evidence), and probably increases treatment-related adverse events such as dysgeusia and diarrhoea during the study period compared to SoC plus placebo (RR 2.06, 95% CI 1.44 to 2.95; 1 study, 2224 participants; moderate-certainty evidence). Nirmatrelvir/ritonavir plus SoC probably decreases discontinuation of study drug due to adverse events compared to SoC plus placebo (RR 0.49, 95% CI 0.30 to 0.80; 1 study, 2224 participants; moderate-certainty evidence). No studies reported improvement of clinical status, quality of life, or viral clearance. Nirmatrelvir/ritonavir for treating people with moderate to severe COVID-19 in inpatient settings We are uncertain whether nirmatrelvir/ritonavir plus SoC compared to SoC reduces all-cause mortality at 28 days (RR 0.63, 95% CI 0.21 to 1.86; 1 study, 264 participants; very low-certainty evidence), or increases viral clearance at seven days (RR 1.06, 95% CI 0.71 to 1.58; 1 study, 264 participants; very low-certainty evidence) and 14 days (RR 1.05, 95% CI 0.92 to 1.20; 1 study, 264 participants; very low-certainty evidence). No studies reported improvement or worsening of clinical status and quality of life. We did not include data for safety outcomes due to insufficient and inconsistent information. Subgroup analyses for equity For outpatients, the outcome 'admission to hospital or death' was investigated for equity regarding age (less than 65 years versus 65 years or greater) and ethnicity. There were no subgroup differences for age or ethnicity. For inpatients, the outcome 'all-cause mortality' was investigated for equity regarding age (65 years or less versus greater than 65 years). There was no difference between subgroups of age. No further equity-related subgroups were reported, and no subgroups were reported for other outcomes. Nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection (PrEP and PEP) No studies available. AUTHORS' CONCLUSIONS: Low-certainty evidence suggests nirmatrelvir/ritonavir reduces the risk of all-cause mortality and hospital admission or death in high-risk, unvaccinated COVID-19 outpatients infected with the Delta variant of SARS-CoV-2. There is low- to moderate-certainty evidence of the safety of nirmatrelvir/ritonavir. Very low-certainty evidence exists regarding the effects of nirmatrelvir/ritonavir on all-cause mortality and viral clearance in mildly to moderately affected, mostly unvaccinated COVID-19 inpatients infected with the Omicron variant of SARS-CoV-2. Insufficient and inconsistent information prevents the assessment of safety outcomes. No reliable differences in effect size and direction were found regarding equity aspects. There is no available evidence supporting the use of nirmatrelvir/ritonavir for preventing SARS-CoV-2 infection. We are continually updating our search and making search results available on the OSF platform.

High-dose methylprednisolone pulse therapy during refractory COVID-19 acute respiratory distress syndrome: a retrospective observational study.

BACKGROUND: Current COVID-19 guidelines recommend the early use of systemic corticoids for COVID-19 acute respiratory distress syndrome (ARDS). It remains unknown if high-dose methylprednisolone pulse therapy (MPT) ameliorates refractory COVID-19 ARDS after many days of mechanical ventilation or rapid deterioration with or without extracorporeal membrane oxygenation (ECMO). METHODS: This is a retrospective observational study. Consecutive patients with COVID-19 ARDS treated with a parenteral high-dose methylprednisolone pulse therapy at the intensive care units (ICU) of two University Hospitals between January 1st 2021 and November 30st 2022 were included. Clinical data collection was at ICU admission, start of MPT, 3-, 10- and 14-days post MPT. RESULTS: Thirty-seven patients (mean age 55 ± 12 years) were included in the study. MPT started at a mean of 17 ± 12 days after mechanical ventilation. Nineteen patients (54%) received ECMO support when commencing MPT. Mean paO2/FiO2 significantly improved 3- (p = 0.034) and 10 days (p = 0.0313) post MPT. The same applied to the necessary FiO2 10 days after MPT (p = 0.0240). There were no serious infectious complications. Twenty-four patients (65%) survived to ICU discharge, including 13 out of 20 (65%) needing ECMO support. CONCLUSIONS: Late administration of high-dose MPT in a critical subset of refractory COVID-19 ARDS patients improved respiratory function and was associated with a higher-than-expected survival of 65%. These data suggest that high-dose MPT may be a viable salvage therapy in refractory COVID-19 ARDS.

Conventional versus video-assisted laryngoscopy for perioperative endotracheal intubation (COVALENT) - a randomized, controlled multicenter trial.

BACKGROUND: Data on the routine use of video-assisted laryngoscopy in peri-operative intubations are rather inconsistent and ambiguous, in part due to small populations and non-uniform outcome measures in past trials. Failed or prolonged intubation procedures are a reason for relevant morbidity and mortality. This study aims to determine whether video-assisted laryngoscopy (with both Macintosh-shaped and hyperangulated blades) is at least equal to the standard method of direct laryngoscopy with respect to the first-pass success rate. Furthermore, validated tools from the field of human factors will be applied to examine within-team communication and task load during this critical medical procedure. METHODS: In this randomized, controlled, three-armed parallel group design, multi-centre trial, a total of more than 2500 adult patients scheduled for perioperative endotracheal intubation will be randomized. In equally large arms, video-assisted laryngoscopy with a Macintosh-shaped or a hyperangulated blade will be compared to the standard of care (direct laryngoscopy with Macintosh blade). In a pre-defined hierarchical analysis, we will test the primary outcome for non-inferiority first. If this goal should be met, the design and projected statistical power also allow for subsequent testing for superiority of one of the interventions. Various secondary outcomes will account for patient safety considerations as well as human factors interactions within the provider team and will allow for further exploratory data analysis and hypothesis generation. DISCUSSION: This randomized controlled trial will provide a solid base of data in a field where reliable evidence is of major clinical importance. With thousands of endotracheal intubations performed every day in operating rooms around the world, every bit of performance improvement translates into increased patient safety and comfort and may eventually prevent significant burden of disease. Therefore, we feel confident that a large trial has the potential to considerably benefit patients and anaesthetists alike. TRIAL REGISTRATION: ClincalTrials.gov NCT05228288. PROTOCOL VERSION: 1.1, November 15, 2021.

Guiding Attention via a Cognitive Aid During a Simulated In-Hospital Cardiac Arrest Scenario: A Salience Effort Expectancy Value Model Analysis.

OBJECTIVE: To investigate the effect of a cognitive aid on the visual attention distribution of the operator using the Salience Effort Expectancy Value (SEEV) model. BACKGROUND: Cognitive aids aim to support an operator during the execution of a task. The effect of cognitive aids on performance is frequently evaluated but whether a cognitive aid improved, for example, attention distribution has not been considered. METHOD: We built the Expectancy Value (EV) model version which can be considered to indicate optimal attention distribution for a given event. We analyzed the eye tracking data of emergency physicians while using a cognitive aid application versus no application during a simulated in-hospital cardiac arrest scenario. RESULTS: The EV model could fit the attention distribution in such a simulated emergency situation. Partially supporting our hypothesis, the cognitive aid application group showed a significantly better EV model fit than the no application group in the first phases of the event, but a worse fit in the last phase. CONCLUSION: We demonstrated that a cognitive aid affected attention distribution and that the SEEV model provides the means of capturing these effects. We suggest that the aid supported and improved visual attention distribution in the stressful first phases of a cardiopulmonary resuscitation but may have focused attention on objects that are relevant for lower priority goals in the last phase. APPLICATION: The SEEV model can provide insights into expected and unexpected effects of cognitive aids on visual attention distribution and may help to design better artifacts.

Effects of Different Hemoglobin Levels on Near-Infrared Spectroscopy-Derived Cerebral Oxygen Saturation in Elderly Patients Undergoing Noncardiac Surgery.

Background: Near-infrared spectroscopy (NIRS) is a commonly used technique to evaluate tissue oxygenation and prevent harmful cerebral desaturation in the perioperative setting. The aims of the present study were to assess whether surgery-related anemia can be detected via NIRS of cerebral oxygen saturation and to investigate the effects of different perioperative transfusion strategies on cerebral oxygenation, potentially affecting transfusion decision-making. Study Design and Methods: Data from the ongoing multicenter LIBERAL-Trial (liberal transfusion strategy to prevent mortality and anemia-associated ischemic events in elderly noncardiac surgical patients, LIBERAL) were used. In this single-center sub-study, regional cerebral oxygenation saturation (rSO2) was evaluated by NIRS at baseline, pre-, and post-RBC transfusion. The obtained values were correlated with blood gas analysis-measured Hb concentrations. Results: rSO2 correlated with Hb decline during surgery (r = 0.35, p < 0.0001). Different RBC transfusion strategies impacted rSO2 such that higher Hb values resulted in higher rSO2. Cerebral desaturation occurred at lower Hb values more often. Discussion: Cerebral oxygenation monitoring using NIRS provides noninvasive rapid and continuous information regarding perioperative alterations in Hb concentration without the utilization of patients' blood for blood sampling. Further investigations are required to demonstrate if cerebral rSO2 may be included in future individualized transfusion decision strategies.

Postoperative nausea and vomiting: risk factors, prediction tools, and algorithms.

PURPOSE OF REVIEW: Postoperative/postdischarge nausea and vomiting (PONV/PDNV) remain relevant issues in perioperative care. Especially in ambulatory surgery, PONV can prevent discharge or lead to unplanned readmission. RECENT FINDINGS: The evidence for the management of PONV is now quite good but is still inadequately implemented. A universal, multimodal rather than risk-adapted approach for PONV prophylaxis is now recommended. The evidence on PDNV is insufficient. SUMMARY: PDNV management is based primarily on consequent prophylaxis and therapy of PONV.

Current concepts in preoperative anemia management in obstetrics.

PURPOSE OF REVIEW: The purpose of this article is to provide an overview of currently recommended treatment approaches for anemia during pregnancy, with a special focus on iron deficiency and iron deficiency anemia (IDA). RECENT FINDINGS: As consistent patient blood management (PBM) guidelines in obstetrics are still lacking, recommendations regarding the timing of anemia screening and the treatment recommendations for iron deficiency and IDA during pregnancy are still controversial. Based on increasing evidence, early screening for anemia and iron deficiency should be recommended at the beginning of each pregnancy. To reduce maternal and fetal burden, any iron deficiency, even without anemia, should be treated as early as possible during pregnancy. While oral iron supplements administered every other day are the standard treatment in the first trimester, the use of intravenous iron supplements is increasingly suggested from the second trimester onwards. SUMMARY: The treatment of anemia, and more specifically iron deficiency anemia during pregnancy, holds many possibilities for improvement. The fact that the period of risk is known well in advance and thus there is a long optimization phase is per se an ideal prerequisite for the best possible therapy of treatable causes of anemia. Standardization of recommendations and guidelines for screening and treatment of IDA in obstetrics is required for the future. In any case, a multidisciplinary consent is the precondition for a successfully implementation of anemia management in obstetrics to establish an approved algorithm easily enabling detection and treatment of IDA during pregnancy.

Is a Patient Blood Management programme economically reasonable?

PURPOSE OF REVIEW: The value of healthcare is defined as the achieved health outcome in relation to the incurred costs. Patient Blood Management (PBM) is a multidisciplinary, evidence-based and patient-centred concept to optimize the patients' red blood cell mass, minimize blood loss and bleeding and to secure the physiological reserve, including the promotion of evidence-based transfusion strategies. This review describes the healthcare value and the cost effectiveness of single PBM measures as well as the implementation of comprehensive PBM programmes. RECENT FINDINGS: Overall, measures improving surgical outcome and reducing hospital length of stay, such as intravenous iron supplementation in iron deficient anaemic patients, the use of antifibrinolytic agents for the treatment of bleeding, the use of cell salvage and adherence to an evidence-based transfusion strategy, are associated with cost savings. SUMMARY: Although several single PBM measures have been shown to be effective and cost-efficient, it remains challenging to compare the results among differing healthcare systems.