The cost-effectiveness of procalcitonin for guiding antibiotic prescribing in individuals hospitalized with COVID-19: part of the PEACH study.

BACKGROUND: Many hospitals introduced procalcitonin (PCT) testing to help diagnose bacterial coinfection in individuals with COVID-19, and guide antibiotic decision-making during the COVID-19 pandemic in the UK. OBJECTIVES: Evaluating cost-effectiveness of using PCT to guide antibiotic decisions in individuals hospitalized with COVID-19, as part of a wider research programme. METHODS: Retrospective individual-level data on patients hospitalized with COVID-19 were collected from 11 NHS acute hospital Trusts and Health Boards from England and Wales, which varied in their use of baseline PCT testing during the first COVID-19 pandemic wave. A matched analysis (part of a wider analysis reported elsewhere) created groups of patients whose PCT was/was not tested at baseline. A model was created with combined decision tree/Markov phases, parameterized with quality-of-life/unit cost estimates from the literature, and used to estimate costs and quality-adjusted life years (QALYs). Cost-effectiveness was judged at a £20 000/QALY threshold. Uncertainty was characterized using bootstrapping. RESULTS: People who had baseline PCT testing had shorter general ward/ICU stays and spent less time on antibiotics, though with overlap between the groups' 95% CIs. Those with baseline PCT testing accrued more QALYs (8.76 versus 8.62) and lower costs (£9830 versus £10 700). The point estimate was baseline PCT testing being dominant over no baseline testing, though with uncertainty: the probability of cost-effectiveness was 0.579 with a 1 year horizon and 0.872 with a lifetime horizon. CONCLUSIONS: Using PCT to guide antibiotic therapy in individuals hospitalized with COVID-19 is more likely to be cost-effective than not, albeit with uncertainty.

A retrospective propensity-score-matched cohort study of the impact of procalcitonin testing on antibiotic use in hospitalized patients during the first wave of COVID-19.

BACKGROUND: Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK. OBJECTIVES: Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic. Secondary: to measure differences in length of hospital/ICU stay, mortality, total days of antibiotic prescribing and resistant bacterial infections between these groups. METHODS: Multi-centre, retrospective, observational, cohort study using patient-level clinical data from acute hospital Trusts/Health Boards in England/Wales. Inclusion: patients ≥16 years, admitted to participating Trusts/Health Boards and with a confirmed positive COVID-19 test between 1 February 2020 and 30 June 2020. RESULTS: Data from 5960 patients were analysed: 1548 (26.0%) had a baseline PCT test and 4412 (74.0%) did not. Using propensity-score matching, baseline PCT testing was associated with an average reduction in early antibiotic prescribing of 0.43 days [95% confidence interval (CI): 0.22-0.64 days, P < 0.001) and of 0.72 days (95% CI: 0.06-1.38 days, P = 0.03] in total antibiotic prescribing. Baseline PCT testing was not associated with increased mortality or hospital/ICU length of stay or with the rate of antimicrobial-resistant secondary bacterial infections. CONCLUSIONS: Baseline PCT testing appears to have been an effective antimicrobial stewardship tool early in the pandemic: it reduced antibiotic prescribing without evidence of harm. Our study highlights the need for embedded, rapid evaluations of infection diagnostics in the National Health Service so that even in challenging circumstances, introduction into clinical practice is supported by evidence for clinical utility. STUDY REGISTRATION NUMBER: ISRCTN66682918.

Sepsis and case fatality rates and associations with deprivation, ethnicity, and clinical characteristics: population-based case-control study with linked primary care and hospital data in England.

PURPOSE: Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The purpose of the study was to measure the associations of specific exposures (deprivation, ethnicity, and clinical characteristics) with incident sepsis and case fatality. METHODS: Two research databases in England were used including anonymized patient-level records from primary care linked to hospital admission, death certificate, and small-area deprivation. Sepsis cases aged 65-100 years were matched to up to six controls. Predictors for sepsis (including 60 clinical conditions) were evaluated using logistic and random forest models; case fatality rates were analyzed using logistic models. RESULTS: 108,317 community-acquired sepsis cases were analyzed. Severe frailty was strongly associated with the risk of developing sepsis (crude odds ratio [OR] 14.93; 95% confidence interval [CI] 14.37-15.52). The quintile with most deprived patients showed an increased sepsis risk (crude OR 1.48; 95% CI 1.45-1.51) compared to least deprived quintile. Strong predictors for sepsis included antibiotic exposure in prior 2 months, being house bound, having cancer, learning disability, and diabetes mellitus. Severely frail patients had a case fatality rate of 42.0% compared to 24.0% in non-frail patients (adjusted OR 1.53; 95% CI 1.41-1.65). Sepsis cases with recent prior antibiotic exposure died less frequently compared to non-users (adjusted OR 0.7; 95% CI 0.72-0.76). Case fatality strongly decreased over calendar time. CONCLUSION: Given the variety of predictors and their level of associations for developing sepsis, there is a need for prediction models for risk of developing sepsis that can help to target preventative antibiotic therapy.

Microbial Volatiles as Diagnostic Biomarkers of Bacterial Lung Infection in Mechanically Ventilated Patients.

BACKGROUND: Early and accurate recognition of respiratory pathogens is crucial to prevent increased risk of mortality in critically ill patients. Microbial-derived volatile organic compounds (mVOCs) in exhaled breath could be used as noninvasive biomarkers of infection to support clinical diagnosis. METHODS: In this study, we investigated the diagnostic potential of in vitro-confirmed mVOCs in the exhaled breath of patients under mechanical ventilation from the BreathDx study. Samples were analyzed by thermal desorption-gas chromatography-mass spectrometry. RESULTS: Pathogens from bronchoalveolar lavage (BAL) cultures were identified in 45 of 89 patients and Staphylococcus aureus was the most commonly identified pathogen (n = 15). Of 19 mVOCs detected in the in vitro culture headspace of 4 common respiratory pathogens (S. aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli), 14 were found in exhaled breath samples. Higher concentrations of 2 mVOCs were found in the exhaled breath of patients infected with S. aureus compared to those without (3-methylbutanal: P < .01, area under the receiver operating characteristic curve [AUROC] = 0.81-0.87; and 3-methylbutanoic acid: P = .01, AUROC = 0.79-0.80). In addition, bacteria identified from BAL cultures that are known to metabolize tryptophan (E. coli, Klebsiella oxytoca, and Haemophilus influenzae) were grouped and found to produce higher concentrations of indole compared to breath samples with culture-negative (P = .034) and other pathogen-positive (P = .049) samples. CONCLUSIONS: This study demonstrates the capability of using mVOCs to detect the presence of specific pathogen groups with potential to support clinical diagnosis. Although not all mVOCs were found in patient samples within this small pilot study, further targeted and qualitative investigation is warranted using multicenter clinical studies.

Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID.

BACKGROUND: COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID). METHODS: We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury. RESULTS: Monocyte alterations in acute COVID-19 patients included aberrant expression of leukocyte migration molecules, continuing into convalescence (n=142) and corresponding with specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of C-X-C motif chemokine receptor 6 (CXCR6) (p<0.0001) and adhesion molecule P-selectin glycoprotein ligand 1 (p<0.01), alongside preferential migration of monocytes towards the CXCR6 ligand C-X-C motif chemokine ligand 16 (CXCL16) (p<0.05), which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in patients with progressive fibrosing interstitial lung disease (p<0.001), confirming a role for the CXCR6-CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited a sustained reduction of the prostaglandin-generating enzyme cyclooxygenase 2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in respiratory syncytial virus or influenza A convalescence. CONCLUSIONS: Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.

Use of hospital services by patients with chronic conditions in sub-Saharan Africa: a systematic review and meta-analysis.

Objective: To estimate the prevalence of individual chronic conditions and multimorbidity among adults admitted to hospital in countries in sub-Saharan Africa. Methods: We systematically searched MEDLINE®, Embase®, Global Index Medicus, Global Health and SciELO for publications reporting on patient cohorts recruited between 1 January 2010 and 12 May 2023. We included articles reporting prevalence of pre-specified chronic diseases within unselected acute care services (emergency departments or medical inpatient settings). No language restrictions were applied. We generated prevalence estimates using random-effects meta-analysis alongside 95% confidence intervals, 95% prediction intervals and I2 statistics for heterogeneity. To explore associations with age, sex, country-level income status, geographical region and risk of bias, we conducted pre-specified meta-regression, sub-group and sensitivity analyses. Findings: Of 6976 identified studies, 61 met the inclusion criteria, comprising data from 20 countries and 376 676 people. None directly reported multimorbidity, but instead reported prevalence for individual conditions. Among medical admissions, the highest prevalence was human immunodeficiency virus infection (36.4%; 95% CI: 31.3-41.8); hypertension (24.4%; 95% CI: 16.7-34.2); diabetes (11.9%; 95% CI: 9.9-14.3); heart failure (8.2%; 95% CI: 5.6-11.9); chronic kidney disease (7.7%; 95% CI: 3.9-14.7); and stroke (6.8%; 95% CI: 4.7-9.6). Conclusion: Among patients seeking hospital care in sub-Saharan Africa, multimorbidity remains poorly described despite high burdens of individual chronic diseases. Prospective public health studies of multimorbidity burden are needed to generate integrated and context-specific health system interventions that act to maximize patient survival and well-being.

Antibacterial effects in blood irradiated with a polychromatic device mediated through reactive oxygen species: possible involvement of haem.

The antibacterial effects of a polychromatic light device designed for intravenous application were assessed in vitro. Staphylococcus aureus, Klebsiella pneumoniae, or Escherichia coli were exposed to a 60-min sequential light cycle comprising 365, 530, and 630 nm wavelengths in circulated sheep blood. Bacteria were quantified by viable counting. The potential involvement of reactive oxygen species in the antibacterial effect was assessed using the antioxidant N-acetylcysteine-amide. A modified device was then used to determine the effects of the individual wavelengths. Exposure of blood to the standard wavelength sequence caused small (c. 0.5 Log 10 CFU) but statistically significant reductions in viable counts for all three bacteria, which were prevented by the addition of N-acetylcysteine-amide. Bacterial inactivation did not occur in blood-free medium, but supplementation with haem restored the moderate bactericidal effect. In single-wavelength experiments, bacterial inactivation occurred only with red (630 nm) light. Concentrations of reactive oxygen species were significantly higher under light stimulation than in unstimulated controls. In summary, exposure of bacteria within blood to a cycle of visible light wavelengths resulted in small but statistically significant bacterial inactivation apparently mediated by a 630 nm wavelength only, via reactive oxygen species possibly generated by excitation of haem groups.

SARS-CoV-2 environmental contamination from hospitalised patients with COVID-19 receiving aerosol-generating procedures.

BACKGROUND: Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered 'aerosol-generating procedures' in the treatment of COVID-19. OBJECTIVE: To measure air and surface environmental contamination with SARS-CoV-2 virus when CPAP and HFNO are used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients. METHODS: 30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.4 to maintain oxygen saturation ≥94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. Real-time quantitative polymerase chain reaction analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus. RESULTS: Overall 21/30 (70%) participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination than supplemental oxygen use. Only one nasopharyngeal sample was culture positive. CONCLUSIONS: The use of CPAP and HFNO to treat moderate/severe COVID-19 did not appear to be associated with substantially higher levels of air or surface viral contamination in the immediate care environment, compared with the use of supplemental oxygen.

Untargeted Molecular Analysis of Exhaled Breath as a Diagnostic Test for Ventilator-Associated Lower Respiratory Tract Infections (BreathDx).

Patients suspected of ventilator-associated lower respiratory tract infections (VA-LRTIs) commonly receive broad-spectrum antimicrobial therapy unnecessarily. We tested whether exhaled breath analysis can discriminate between patients suspected of VA-LRTI with confirmed infection, from patients with negative cultures. Breath from 108 patients suspected of VA-LRTI was analysed by gas chromatography-mass spectrometry. The breath test had a sensitivity of 98% at a specificity of 49%, confirmed with a second analytical method. The breath test had a negative predictive value of 96% and excluded pneumonia in half of the patients with negative cultures. Trial registration number: UKCRN ID number 19086, registered May 2015.

RAND appropriateness panel to determine the applicability of UK guidelines on the management of acute respiratory distress syndrome (ARDS) and other strategies in the context of the COVID-19 pandemic.

BACKGROUND: COVID-19 has become the most common cause of acute respiratory distress syndrome (ARDS) worldwide. Features of the pathophysiology and clinical presentation partially distinguish it from 'classical' ARDS. A Research and Development (RAND) analysis gauged the opinion of an expert panel about the management of ARDS with and without COVID-19 as the precipitating cause, using recent UK guidelines as a template. METHODS: An 11-person panel comprising intensive care practitioners rated the appropriateness of ARDS management options at different times during hospital admission, in the presence or absence of, or varying severity of SARS-CoV-2 infection on a scale of 1-9 (where 1-3 is inappropriate, 4-6 is uncertain and 7-9 is appropriate). A summary of the anonymised results was discussed at an online meeting moderated by an expert in RAND methodology. The modified online survey comprising 76 questions, subdivided into investigations (16), non-invasive respiratory support (18), basic intensive care unit management of ARDS (20), management of refractory hypoxaemia (8), pharmacotherapy (7) and anticoagulation (7), was completed again. RESULTS: Disagreement between experts was significant only when addressing the appropriateness of diagnostic bronchoscopy in patients with confirmed or suspected COVID-19. Adherence to existing published guidelines for the management of ARDS for relevant evidence-based interventions was recommended. Responses of the experts to the final survey suggested that the supportive management of ARDS should be the same, regardless of a COVID-19 diagnosis. For patients with ARDS with COVID-19, the panel recommended routine treatment with corticosteroids and a lower threshold for full anticoagulation based on a high index of suspicion for venous thromboembolic disease. CONCLUSION: The expert panel found no reason to deviate from the evidence-based supportive strategies for managing ARDS outlined in recent guidelines.

The accuracy of pulse oximetry in measuring oxygen saturation by levels of skin pigmentation: a systematic review and meta-analysis.

BACKGROUND: During the COVID-19 pandemic, there have been concerns regarding potential bias in pulse oximetry measurements for people with high levels of skin pigmentation. We systematically reviewed the effects of skin pigmentation on the accuracy of oxygen saturation measurement by pulse oximetry (SpO2) compared with the gold standard SaO2 measured by CO-oximetry. METHODS: We searched Ovid MEDLINE, Ovid Embase, EBSCO CINAHL, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform (up to December 2021) for studies with SpO2-SaO2 comparisons and measuring the impact of skin pigmentation or ethnicity on pulse oximetry accuracy. We performed meta-analyses for mean bias (the primary outcome in this review) and its standard deviations (SDs) across studies included for each subgroup of skin pigmentation and ethnicity and used these pooled mean biases and SDs to calculate accuracy root-mean-square (Arms) and 95% limits of agreement. The review was registered with the Open Science Framework ( https://osf.io/gm7ty ). RESULTS: We included 32 studies (6505 participants): 15 measured skin pigmentation and 22 referred to ethnicity. Compared with standard SaO2 measurement, pulse oximetry probably overestimates oxygen saturation in people with the high level of skin pigmentation (pooled mean bias 1.11%; 95% confidence interval 0.29 to 1.93%) and people described as Black/African American (1.52%; 0.95 to 2.09%) (moderate- and low-certainty evidence). The bias of pulse oximetry measurements for people with other levels of skin pigmentation or those from other ethnic groups is either more uncertain or suggests no overestimation. Whilst the extent of mean bias is small or negligible for all subgroups evaluated, the associated imprecision is unacceptably large (pooled SDs > 1%). When the extent of measurement bias and precision is considered jointly, pulse oximetry measurements for all the subgroups appear acceptably accurate (with Arms < 4%). CONCLUSIONS: Pulse oximetry may overestimate oxygen saturation in people with high levels of skin pigmentation and people whose ethnicity is reported as Black/African American, compared with SaO2. The extent of overestimation may be small in hospital settings but unknown in community settings. REVIEW PROTOCOL REGISTRATION: https://osf.io/gm7ty.

Composition and diversity analysis of the lung microbiome in patients with suspected ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) is associated with high morbidity and health care costs, yet diagnosis remains a challenge. Analysis of airway microbiota by amplicon sequencing provides a possible solution, as pneumonia is characterised by a disruption of the microbiome. However, studies evaluating the diagnostic capabilities of microbiome analysis are limited, with a lack of alignment on possible biomarkers. Using bronchoalveolar lavage fluid (BALF) from ventilated adult patients suspected of VAP, we aimed to explore how key characteristics of the microbiome differ between patients with positive and negative BALF cultures and whether any differences could have a clinically relevant role. METHODS: BALF from patients suspected of VAP was analysed using 16s rRNA sequencing in order to: (1) differentiate between patients with and without a positive culture; (2) determine if there was any association between microbiome diversity and local inflammatory response; and (3) correctly identify pathogens detected by conventional culture. RESULTS: Thirty-seven of 90 ICU patients with suspected VAP had positive cultures. Patients with a positive culture had significant microbiome dysbiosis with reduced alpha diversity. However, gross compositional variance was not strongly associated with culture positivity (AUROCC range 0.66-0.71). Patients with a positive culture had a significantly higher relative abundance of pathogenic bacteria compared to those without [0.45 (IQR 0.10-0.84), 0.02 (IQR 0.004-0.09), respectively], and an increased interleukin (IL)-1ß was associated with reduced species evenness (rs = - 0.33, p < 0.01) and increased pathogenic bacteria presence (rs = 0.28, p = 0.013). Untargeted 16s rRNA pathogen detection was limited by false positives, while the use of pathogen-specific relative abundance thresholds showed better diagnostic accuracy (AUROCC range 0.89-0.998). CONCLUSION: Patients with positive BALF culture had increased dysbiosis and genus dominance. An increased caspase-1-dependent IL-1b expression was associated with a reduced species evenness and increased pathogenic bacterial presence, providing a possible causal link between microbiome dysbiosis and lung injury development in VAP. However, measures of diversity were an unreliable predictor of culture positivity and 16s sequencing used agnostically could not usefully identify pathogens; this could be overcome if pathogen-specific relative abundance thresholds are used.

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration: isrctn.org Identifier: ISRCTN16912075.

The multidisciplinary team perspectives on agitation management in critical care: A qualitative study.

BACKGROUND: People who are experiencing a period of critical illness frequently experience severe agitation. The presence of agitation can pose risks to the patient, family, and clinical team. AIMS AND OBJECTIVES: To capture the views and opinions of critical care multidisciplinary teams concerning the approaches in the management of agitation, and to understand and identify the perceived risks and benefits of current management strategies. DESIGN: A descriptive qualitative design. METHODS: Data were gathered using semi-structured interviews with multidisciplinary teams from adult critical care units from one region in the United Kingdom. FINDINGS: A total of 19 participants participated between February to September 2017. There were two group interviews (GIs) (n = 12, GI 1 n =  8, GI 2 n = 4) and seven one-to-one interviews, across four hospital organisations with one participant working via an agency. The mean length (± SD) of each interview, one to one or group, was 58.86 minutes (5.81 minutes). Three major themes were generated about the complex clinical decision-making required to manage an agitated patient. These themes represented: the burden of care, continuity of clinical decision-making, and uncertainty and indecision experienced by participants. CONCLUSION: Participants described caring for an agitated patient as challenging and stressful. Staff sought clarification on what level of restrictive practice is allowed. Feelings of anxiety and stress generated by the decisions made may have an impact on staff, particularly those who are more inexperienced, which in the longer term could lead to fatigue or moral distress. RELEVANCE TO CLINICAL PRACTICE: The study has emphasised the challenges faced by multidisciplinary teams and how decision-making may impact on individuals within the team.

Critically ill patients' experience of agitation: A qualitative meta-synthesis.

BACKGROUND: Acute episodes of agitation are frequently experienced by patients during critical illness, yet what is not understood is the experience of agitation from the patient and family perspectives. AIMS AND OBJECTIVES: To search existing literature, appraise it and then provide a synthesized interpretation to broaden the understanding of patients' and their families' experience of agitation during an adult critical care admission. DESIGN: Qualitative meta-synthesis. METHODS: A qualitative meta-synthesis based on a systematic literature search registered with PROSPERO. The search conducted between July and September 2019 was applied to ProQuest, Cumulative Index to Nursing and Allied Health, British Nursing Index, Cochrane Library, Ovid Medline, Web of Science, and PsycINFO databases. We appraised the selected literature and presented a synthesized interpretation. Analysis was based on the approach of Gadamerian hermeneutics. Due to the lack of data identified; the family experiences of agitation could not be addressed within the review. RESULTS: In total, 8 studies were included capturing the experiences of 494 patients, aged between 18 and 92 years, with 225 (45%) women. The analysis generated three core themes: (a) What is real, what is not, (b) loss of communication and dependency, and (c) what helps, what does not. Fear of death, the emotion of anxiety, and feelings of pain alongside transient periods of fluctuating conscious levels provoked a feeling of intense vulnerability. The loss of effective communication and the feeling of dependence incite agitation and distress. CONCLUSIONS: The patient's recollection of their critical illness can be completely or partially absent and disjointed with uncertainty around what is real and what is not. Family members observe the full effect of the patient's critical care illness and could be a wealth of untapped information. RELEVANCE TO CLINICAL PRACTICE: Increasing awareness of the critically ill patients' experience of agitation highlights possible contributing factors to agitation development, such as staff interaction and communication skills, and the critical care environment.

Detection and quantification of exhaled volatile organic compounds in mechanically ventilated patients - comparison of two sampling methods.

Exhaled breath analysis is a promising new diagnostic tool, but currently no standardised method for sampling is available in mechanically ventilated patients. We compared two breath sampling methods, first using an artificial ventilator circuit, then in "real life" in mechanically ventilated patients on the intensive care unit. In the laboratory circuit, a 24-component synthetic-breath volatile organic compound (VOC) mixture was injected into the system as air was sampled: (A) through a port on the exhalation limb of the circuit and (B) through a closed endo-bronchial suction catheter. Sorbent tubes were used to collect samples for analysis by thermal desorption-gas chromatography-mass spectrometry. Realistic mechanical ventilation rates and breath pressure-volume loops were established and method detection limits (MDLs) were calculated for all VOCs. Higher yields of VOCs were retrieved using the closed suction catheter; however, for several VOCs MDLs were compromised due to the background signal associated with plastic and rubber components in the catheters. Different brands of suction catheter were compared. Exhaled VOC data from 40 patient samples collected at two sites were then used to calculate the proportion of data analysed above the MDL. The relative performance of the two methods differed depending on the VOC under study and both methods showed sensitivity towards different exhaled VOCs. Furthermore, method performance differed depending on recruitment site, as the centres were equipped with different brands of respiratory equipment, an important consideration for the design of multicentre studies investigating exhaled VOCs in mechanically ventilated patients.

Healthcare system impacts of the 2017 Manchester Arena bombing: evidence from a national trauma registry patient case series and hospital performance data.

INTRODUCTION: In response to detonation of an improvised explosive device at the Manchester Arena on 22 May 2017, we aimed to use detailed information about injured patients flowing through hospital healthcare to objectively evaluate the preplanned responses of a regional trauma care system and to show how routinely collected hospital performance data can be used to assess impact on regional healthcare. METHODS: Data about injury severity, management and outcome for patients presenting to hospitals were collated using England's major trauma registry for 30 days following hospital attendance. System-wide data about hospital performance were collated by National Health Service England's North West Utilisation Management Unit and presented as Shewhart charts from 15 April 2017 to 25 June 2017. RESULTS: Detailed information was obtained on 153 patients (109 adults and 44 children) who attended hospital emergency departments after the incident. Within 6 hours, a network of 11 regional trauma care hospitals received a total of 138 patients (90%). For the whole patient cohort, median Injury Severity Score (ISS) was 1 (IQR 1-10) and median New ISS (NISS) was 2 (IQR 1-14). For the 75 patients (49%) attending a major trauma centre, median ISS was 7.5 (IQR 1-14) and NISS was 10 (IQR 3-22). Limb and torso body regions predominated when injuries were classified as major life threatening (Abbreviated Injury Scale>3). Ninety-three patients (61%) required hospital admission following emergency department management, with 21 (14%) requiring emergency damage control surgery and 24 (16%) requiring critical care. Three fatalities occurred during early resuscitative treatment and 150 (98%) survived to day 30. The increased system-wide hospital admissions and care activity was linked to increases in regional hospital care capacity through cancellations of elective surgery and increased community care. Consequently, there were sustained system-wide hospital service improvements over the following weeks. CONCLUSIONS: The systematic collation of injured patient and healthcare system data has provided an objective evaluation of a regional major incident plan and provided insight into healthcare system resilience. Hospital patient care data indicated that a prerehearsed patient dispersal plan at incident scene was implemented effectively.

Mucoactive agents for acute respiratory failure in the critically ill: a systematic review and meta-analysis.

PURPOSE: Acute respiratory failure (ARF) is a common cause of admission to intensive care units (ICUs). Mucoactive agents are medications that promote mucus clearance and are frequently administered in patients with ARF, despite a lack of evidence to underpin clinical decision making. The aim of this systematic review was to determine if the use of mucoactive agents in patients with ARF improves clinical outcomes. METHODS: We searched electronic and grey literature (January 2020). Two reviewers independently screened, selected, extracted data and quality assessed studies. We included trials of adults receiving ventilatory support for ARF and involving at least one mucoactive agent compared with placebo or standard care. Outcomes included duration of mechanical ventilation. Meta-analysis was undertaken using random-effects modelling and certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation. RESULTS: Thirteen randomised controlled trials were included (1712 patients), investigating four different mucoactive agents. Mucoactive agents showed no effect on duration of mechanical ventilation (seven trials, mean difference (MD) -1.34, 95% CI -2.97 to 0.29, I2=82%, very low certainty) or mortality, hospital stay and ventilator-free days. There was an effect on reducing ICU length of stay in the mucoactive agent groups (10 trials, MD -3.22, 95% CI -5.49 to -0.96, I2=89%, very low certainty). CONCLUSION: Our findings do not support the use of mucoactive agents in critically ill patients with ARF. The existing evidence is of low quality. High-quality randomised controlled trials are needed to determine the role of specific mucoactive agents in critically ill patients with ARF. PROSPERO REGISTRATION NUMBER: CRD42018095408.

The effectiveness of frequent antibiotic use in reducing the risk of infection-related hospital admissions: results from two large population-based cohorts.

BACKGROUND: Previous research reported that individuals prescribed antibiotics frequently develop antimicrobial resistance. The objective of this study was to evaluate whether frequent antibiotic use is associated with reduced hospital admissions for infection-related complications. METHODS: Population-based cohort study analysing electronic health records from primary care linked to hospital admission records. The study population included patients prescribed a systemic antibiotic, recent record of selected infections and no history of chronic obstructive pulmonary disease. Propensity-matched cohorts were identified based on quintiles of prior antibiotic use in 3 years before. RESULTS: A total of 1.8 million patients were included. Repeated antibiotic use was frequent. The highest rates of hospital admissions for infection-related complications were observed shortly after antibiotic start in all prior exposure quintiles. For patients with limited prior antibiotic use, rates then dropped quickly and substantially. In contrast, reductions over time were substantially less in patients with frequent prior antibiotic use, with rates remaining elevated over the following 6 months. In patients without comorbidity comparing the highest to lowest prior exposure quintiles in the Clinical Practice Research Databank, the IRRs were 1.18 [95% CI 0.90-1.55] in the first 3 days after prescription, 1.44 [95% CI 1.14-1.81] in the days 4-30 after and 3.22 [95% CI 2.29-4.53] in the 3-6 months after. CONCLUSIONS: Repeated courses of antibiotics, although common practice, may have limited benefit and indicator of adverse outcomes. A potential mechanism is that antibiotics may cause dysbiosis (perturbations of intestinal microbiota), contributing to colonization with resistant bacteria. Antibiotics should be used judiciously and only periodically unless indicated. Antimicrobial stewardship should include activities focusing on the substantive number of patients who repeatedly but intermittently get antibiotics.

Understanding and Enhancing Sepsis Survivorship. Priorities for Research and Practice.

An estimated 14.1 million patients survive sepsis each year. Many survivors experience poor long-term outcomes, including new or worsened neuropsychological impairment; physical disability; and vulnerability to further health deterioration, including recurrent infection, cardiovascular events, and acute renal failure. However, clinical trials and guidelines have focused on shorter-term survival, so there are few data on promoting longer-term recovery. To address this unmet need, the International Sepsis Forum convened a colloquium in February 2018 titled "Understanding and Enhancing Sepsis Survivorship." The goals were to identify gaps and limitations of current research and shorter- and longer-term priorities for understanding and enhancing sepsis survivorship. Twenty-six experts from eight countries participated. The top short-term priorities identified by nominal group technique culminating in formal voting were to better leverage existing databases for research, develop and disseminate educational resources on postsepsis morbidity, and partner with sepsis survivors to define and achieve research priorities. The top longer-term priorities were to study mechanisms of long-term morbidity through large cohort studies with deep phenotyping, build a harmonized global sepsis registry to facilitate enrollment in cohorts and trials, and complete detailed longitudinal follow-up to characterize the diversity of recovery experiences. This perspective reviews colloquium discussions, the identified priorities, and current initiatives to address them.