Hospital length of stay for COVID-19 patients: Data-driven methods for forward planning.

BACKGROUND: Predicting hospital length of stay (LoS) for patients with COVID-19 infection is essential to ensure that adequate bed capacity can be provided without unnecessarily restricting care for patients with other conditions. Here, we demonstrate the utility of three complementary methods for predicting LoS using UK national- and hospital-level data. METHOD: On a national scale, relevant patients were identified from the COVID-19 Hospitalisation in England Surveillance System (CHESS) reports. An Accelerated Failure Time (AFT) survival model and a truncation corrected method (TC), both with underlying Weibull distributions, were fitted to the data to estimate LoS from hospital admission date to an outcome (death or discharge) and from hospital admission date to Intensive Care Unit (ICU) admission date. In a second approach we fit a multi-state (MS) survival model to data directly from the Manchester University NHS Foundation Trust (MFT). We develop a planning tool that uses LoS estimates from these models to predict bed occupancy. RESULTS: All methods produced similar overall estimates of LoS for overall hospital stay, given a patient is not admitted to ICU (8.4, 9.1 and 8.0 days for AFT, TC and MS, respectively). Estimates differ more significantly between the local and national level when considering ICU. National estimates for ICU LoS from AFT and TC were 12.4 and 13.4 days, whereas in local data the MS method produced estimates of 18.9 days. CONCLUSIONS: Given the complexity and partiality of different data sources and the rapidly evolving nature of the COVID-19 pandemic, it is most appropriate to use multiple analysis methods on multiple datasets. The AFT method accounts for censored cases, but does not allow for simultaneous consideration of different outcomes. The TC method does not include censored cases, instead correcting for truncation in the data, but does consider these different outcomes. The MS method can model complex pathways to different outcomes whilst accounting for censoring, but cannot handle non-random case missingness. Overall, we conclude that data-driven modelling approaches of LoS using these methods is useful in epidemic planning and management, and should be considered for widespread adoption throughout healthcare systems internationally where similar data resources exist.

Maternal heart rate during the first 48h postpartum: a retrospective cross sectional study.

OBJECTIVES: 1) Describe the distribution of heart rate in the first 48h postpartum in women with no evidence of sepsis, anaemia or haemorrhage. 2) Investigate the relationship between postpartum heart rate and other maternal factors. STUDY DESIGN: A retrospective cross-sectional study of postpartum women who delivered between July 2012 and June 2015 in a tertiary hospital. Data was analysed from the local maternity system and electronic vital signs database. The main outcome measures: Heart rate at 6, 12, 24 and 48h postpartum. RESULTS: Data were obtained on 11401 women. After exclusion of women with possible sepsis, anaemia or haemorrhage, 7627 heart rate readings from 5164 women were analysed. Mean heart rate (+2SD/+3SD) at 6h was 83.6 (108.2/120.6), 12h 84.5 (109.4/121.9), 24h 85.4 (110.4/122.9), and 48h 84.3 (109.7/122.4). There was statistical correlation of post partum heart rate with body mass index (BMI), age and discharge haemoglobin. CONCLUSION: This study describes the distribution of maternal heart rate in the early postpartum period, in women with no evidence of sepsis, anaemia or major haemorrhage. This will facilitate identification and appropriate investigation of women with abnormal heart rates. Although correlation with BMI, age and discharge haemoglobin was demonstrated, the differences were small and not clinically meaningful. Further work investigating the relationship between postpartum heart rate and poor maternal outcomes is required.

Twenty-four hour infusion of human recombinant activated protein C (Xigris) early in severe acute pancreatitis: The XIG-AP 1 trial.

OBJECTIVE: Patients with severe acute pancreatitis were excluded from major trials of human recombinant activated protein C (Xigris) because of concern about pancreatic haemorrhage although these individuals have an intense systemic inflammatory response that may benefit from treatment. The object of this study was to provide initial safety data evaluating Xigris in severe acute pancreatitis. DESIGN: Prospective clinical trial recruiting between November 2009 and October 2011. Patients received human recombinant activated protein C (Xigris) for 24 h by intravenous infusion (24 µg/kg/h) in addition to standard clinical care. A matched historical control group treated within the same hospital unit were used to compare outcomes. Of 166 consecutive admitted patients, 43 met the screening criteria for severe acute pancreatitis and 19 were recruited, all contributing to the analyses. RESULTS: Compared to historical controls, there were fewer bleeding events in the Xigris group although the finding did not reach significance (Xigris 0% vs. Control 21%, p = 0.13), similarly further intervention appeared less frequent (11% vs. 47%, p = 0.07) in the treatment group. Length of stay was shorter for patients receiving Xigris (19 vs. 41 days, p = 0.03) as was inotrope use (5% vs. 32%, p = 0.02); mortality and incidence of infections in both groups were similar. Biomarker protein C increased while IL-6 decreased following infusion. CONCLUSIONS: A 24-hr infusion of Xigris appears safe when used in patients with severe acute pancreatitis. TRIAL REGISTRATION: Eudract Number 2007-003635-23.

'Matching Michigan': a 2-year stepped interventional programme to minimise central venous catheter-blood stream infections in intensive care units in England.

BACKGROUND: Bloodstream infections from central venous catheters (CVC-BSIs) increase morbidity and costs in intensive care units (ICUs). Substantial reductions in CVC-BSI rates have been reported using a combination of technical and non-technical interventions. METHODS: We conducted a 2-year, four-cluster, stepped non-randomised study of technical and non-technical (behavioural) interventions to prevent CVC-BSIs in adult and paediatric ICUs in England. Random-effects Poisson regression modelling was used to compare infection rates. A sample of ICUs participated in data verification. RESULTS: Of 223 ICUs in England, 215 (196 adult, 19 paediatric) submitted data on 2479 of 2787 possible months and 147 (66%) provided complete data. The exposure rate was 438 887 (404 252 adult and 34 635 paediatric) CVC-patient days. Over 20 months, 1092 CVC-BSIs were reported. Of these, 884 (81%) were ICU acquired. For adult ICUs, the mean CVC-BSI rate decreased over 20 months from 3.7 in the first cluster to 1.48 CVC-BSIs/1000 CVC-patient days (p<0.0001) for all clusters combined, and for paediatric ICUs from 5.65 to 2.89 (p=0.625). The trend for infection rate reduction did not accelerate following interventions training. CVC utilisation rates remained stable. Pre-ICU infections declined in parallel with ICU-acquired infections. Criterion-referenced case note review showed high agreement between adjudicators (κ 0.706) but wide variation in blood culture sampling rates and CVC utilisation. Generic infection control practices varied widely. CONCLUSIONS: The marked reduction in CVC-BSI rates in English ICUs found in this study is likely part of a wider secular trend for a system-wide improvement in healthcare-associated infections. Opportunities exist for greater harmonisation of infection control practices. Future studies should investigate causal mechanisms and contextual factors influencing the impact of interventions directed at improving patient care.

Exercise testing in survivors of intensive care--is there a role for cardiopulmonary exercise testing?

PURPOSE: The aims of this study were to assess the feasibility of cardiopulmonary exercise testing (CPET) for the early assessment of cardiorespiratory fitness in general adult intensive care unit (ICU) survivors and to characterize the pathophysiology of exercise limitation in this population. METHODS: Fifty general ICU survivors (ventilated for ≥ 5 days) performed a maximal cycle ergometer CPET within 6 weeks of hospital discharge. Health-related quality of life was measured by the Medical Outcome Study Short Form 36 version 2.0 questionnaire. RESULTS: Fifty patients (median age, 57 years; median Acute Physiology And Chronic Health Evaluation II score, 16) completed a CPET 24 ± 14 days after hospital discharge with no adverse events. Significant exercise limitation was present with peak Vo(2) 56% ± 16% predicted and anaerobic threshold (AT) 41% ± 13% of peak predicted Vo(2). Prospectively stratified subgroup comparison showed that patients ventilated for 14 days or more had a significantly lower AT and peak Vo(2) than those ventilated for 5 to 14 days (AT: 9.6 vs 11.7 mL/kg per minute O(2), P = .009; peak Vo(2): 12.9 vs 15.3 mL/kg per minute O(2), P = .022). At peak exercise, heart rate reserve was 25% ± 14%, breathing reserve was 47% ± 19%, and the respiratory exchange ratio was 0.96 ± 0.11. Ventilatory equivalents for CO(2) (Eqco(2)) were 39 ± 9. CONCLUSIONS: Significant exercise limitation is evident in patients who have had critical illness. Etiology of exercise limitation appears multifactorial, with general deconditioning and muscle weakness as major contributory factors. Early CPET appears a practical method of assessing exercise capacity in ICU survivors. Cardiopulmonary exercise testing could be used to select patients who may benefit most from a targeted physical rehabilitation program, aid in exercise prescription, and help assess the response to intervention.

Bedside electronic capture of clinical observations and automated clinical alerts to improve compliance with an Early Warning Score protocol.

BACKGROUND: Failure to comply with clinical protocols and failure of communication to ensure delivery of the most appropriate timely clinical responses to patients whose conditions are acutely deteriorating have been shown to be significant causative factors associated with inhospital adverse events. OBJECTIVE: To determine whether automated clinical alerts increase compliance with an Early Warning Score (EWS) protocol and improve patient outcomes. METHODS: We performed a historically controlled study of bedside electronic capture of observations and automated clinical alerts. The primary outcome measure was hospital length of stay (LOS); secondary outcome measures were compliance with the EWS protocol, cardiac arrest incidence, critical care utilisation and hospital mortality. RESULTS: Between baseline and intervention, 1481 consecutive patients were recruited generating 13 668 observation sets. There was a reduction in hospital LOS between the baseline and alert phase (9.7 days v 6.9 days, P < 0.001). EWS accuracy improved from 81% to 100% with electronic calculation. Clinical attendance to patients with EWS 3, 4 or 5 increased from 29% at baseline to 78% with automated alerts (P < 0.001). For patients with an EWS > 5, clinical attendance increased from 67% at baseline to 96% with automatic alerts (P < 0.001). CONCLUSIONS: Electronic recording of patient observations linked to a computer system that calculates patient risk and then issues automatic graded alerts can improve clinical attendance to unstable general medical ward patients.

Cigarette smoke decreases innate responses of epithelial cells to rhinovirus infection.

Exposure to cigarette smoke is associated with a significant increase in the risk for respiratory viral infections. The airway epithelium is the primary target for both cigarette smoke and respiratory viral infection. We investigated the effects of cigarette smoke on the response of airway epithelial cells to rhinovirus infection. We found that pre-exposure of BEAS-2B cells or primary normal human bronchial epithelial cells (NHBEs) to cigarette smoke extract (CSE) reduced the induction of mRNA of the chemokines CXCL10 and CCL5 by either the viral mimic polyinosine-polycytidylic acid (Poly I:C) or human rhinovirus 16 (HRV-16) infection. The HRV-16-induced release of CXCL10 and CCL5 was also significantly suppressed by CSE. Activation of the IFN mediator STAT-1 and the activation of JNK by poly I:C and HRV-16 were partially suppressed by pre-exposure to CSE. In contrast, the poly I:C-induced and HRV-16-induced phosphorylation of ERK1/2 was unaffected by CSE. HRV-16-stimulated IFN-ß mRNA was also significantly reduced by CSE. Because suppression of the IFN response to viral infection was associated with increased viral production, we assessed HRV-16 RNA concentrations. Exposure to CSE resulted in an increase in HRV-16 RNA at 48 hours after the infection of BEAS-2B cells. These data demonstrate that exposure to CSE alters the response of airway epithelial cells to HRV infection, leading to decreased activation of the IFN-STAT-1 and SAP-JNK pathways, the suppression of CXCL10 and CCL5 production, and increased viral RNA. A diminished, early epithelial-initiated antiviral response to rhinovirus infection could contribute to the increased susceptibility of subjects to prolonged respiratory viral infections after exposure to cigarette smoke.

Gut barrier dysfunction in critically ill surgical patients with abdominal compartment syndrome.

OBJECTIVES: This study investigated the effects of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on gut barrier function in critically ill surgical patients. METHODS: A prospective observational cohort study on patients with severe acute pancreatitis or abdominal sepsis admitted to an intensive care or high-dependency unit. Intra-abdominal pressure (IAP) and plasma levels of immunoglobulin G (IgG) and IgM antiendotoxin core antibodies (EndoCAb) and procalcitonin (ProCT) were measured serially. RESULTS: Among 32 recruited patients, 24 (75%) and 8 patients (25%) developed IAH and ACS, respectively. The state of ACS was associated with significant reductions in plasma IgG EndoCAb (P = 0.015) and IgM EndoCAb (P = 0.016) and higher concentrations of plasma ProCT (P = 0.056) compared with absence of ACS. Resolution of IAH and ACS was associated with significant recovery of plasma IgG EndoCAb (P = 0.003 and P = 0.009, respectively) and IgM EndoCAb (P = 0.002 and P = 0.003, respectively) and reduction in plasma ProCT concentration (P = 0.049 and P = 0.019, respectively). Negative correlations were observed between IAP and plasma IgG EndoCAb (P = 0.003) and IgM EndoCAb (P = 0.002). CONCLUSIONS: Intra-abdominal hypertension and ACS are associated with significantly higher endotoxin exposure and ProCT concentrations, suggestive of gut barrier dysfunction. Resolution of IAH and ACS is associated with evidence for recovery of gut barrier function.

Open pancreatic necrosectomy in the multidisciplinary management of postinflammatory necrosis.

OBJECTIVE: To examine clinical outcome in a consecutive cohort of patients undergoing open necrosectomy for postinflammatory necrosis. BACKGROUND INFORMATION: The last decade has witnessed major developments in the surgical management of pancreatic necrosis. Minimally invasive approaches have become established. However, there are limited data from contemporary open necrosectomy, in particular where multidisciplinary care and aggressive interventional radiology are used. This report provides data on outcome from open necrosectomy in a tertiary referral Hepatobiliary unit over the last decade. METHODS: During the period January 1, 2000 to July 31, 2008, 1535 patients were admitted with a final discharge code of acute pancreatitis. Twenty-eight (1.8%) of all admissions underwent open surgical necrosectomy. Twenty-four (86%) were tertiary referral patients. RESULTS: The median APACHE II score on admission was 10.5 (5-26). Median logistic organ dysfunction score on admission was 3 (0-10). Median LODS score after surgery was 2 (0-8). Twenty patients (71%) underwent radiologically guided drainage of collections before surgery. Thirty-day mortality occurred in 2 (7%), 4 further deaths occurred in patients after discharge from intensive care resulting in a total of 6 (22%) episode-related deaths. CONCLUSIONS: Modern open necrosectomy can be performed without the procedure-related deterioration in organ dysfunction associated with major debridement. Multidisciplinary care with an emphasis on aggressive radiologic intervention before and after surgery results in acceptable outcomes in this cohort of critically ill patients. Newer laparoscopic techniques must demonstrate similar outcomes in the setting of stage-matched severity before wider acceptance.

Regulation of kinin B(2) receptors by bradykinin in human lung cells.

Bradykinin is a potent mediator of inflammation that has been shown to participate in allergic airway inflammation. The biologic effects of bradykinin are mediated by binding and activation of its cognate receptor, the B(2) receptor (B(2)R). In the lung fibroblast cell line IMR-90, binding of bradykinin to B(2)R triggers down-regulation of receptor surface expression, suggesting that bradykinin-induced inflammation is transient and self-limited. Notably, subjects with chronic airway inflammation continue to respond to BK following a first challenge. B(2)Rs are expressed on many different lung cell types, including airway epithelial cells. We therefore compared IMR-90 cells with the human lung epithelial cell line BEAS2B and found that B(2)R expression in the two cell types is differently regulated by BK. Whereas BK induces down-regulation of B(2)R in IMR-90 cells, the same treatment leads to up-regulation of the receptor in BEAS2B cells. These results provide a possible explanation for the potency of bradykinin in inducing ongoing airway inflammation.

Experimental rhinovirus infection increases human tissue kallikrein activation in allergic subjects.

BACKGROUND: Rhinovirus infection is a major cause of asthma exacerbations. While rhinovirus infection is known to generate kinins in the upper respiratory track, little is known about the effect of rhinovirus on kinin generation in the lower airway. We previously identified human tissue kallikrein (hTK) as the principal lung kininogenase during allergic airway inflammation. In this report we investigate the effect of experimental rhinovirus infection on hTK activity in the airways of atopic subjects with and without asthma. METHODS: Eight atopic subjects, 4 with asthma, underwent bronchoscopy with lavage. At least 1 month later, subjects were inoculated with rhinovirus, then underwent repeat bronchoscopy with lavage 4 and 18 days later. hTK mRNA was measured in nasal scrape samples by quantitative real-time PCR. hTK activity (chromogenic substrate assay) and IL-8 levels (ELISA) were assessed in the bronchoalveolar lavage fluid. RESULTS: At day 4 after rhinovirus inoculation, nasal hTK mRNA was modestly increased in both the rhinitis (1.7-fold) and asthmatic (2.1-fold) groups. A doubling or greater increase in hTK activity after rhinovirus infection was observed in all 4 asthmatic subjects (mean 19-fold increase) but only in 1 of 4 atopic subjects without asthma (mean 2-fold increase). Rhinovirus infection also increased the IL-8 protein level in bronchoalveolar lavage fluid, which correlated with hTK activity (R = 0.82). CONCLUSION: Experimental rhinovirus infection in allergic asthmatic subjects is accompanied by increased lower airway hTK activation, which parallels the appearance of IL-8. Rhinovirus-induced hTK activation may contribute to airway inflammation and asthmatic exacerbations.

Clinical relevance of intra-abdominal hypertension in patients with severe acute pancreatitis.

OBJECTIVES: Intra-abdominal hypertension (IAH) contributes to organ failure in patients with abdominal trauma and sepsis and leads to the development of abdominal compartment syndrome (ACS). This study aims to investigate the clinical significance of IAH in patients with severe acute pancreatitis (SAP). METHODS: Patients admitted to intensive care with SAP underwent daily measurement of intra-abdominal pressure (IAP), recording of the clinical data, and calculation of 4 organ dysfunction scores. RESULTS: Among 18 patients with SAP, 11 (61%) developed IAH (median, 20 mm Hg), whereas 10 (56%) developed ACS. The IAP correlated significantly with the 4 organ dysfunction scores; the scores were significantly higher when IAH existed than when it did not. The admission IAP correlated significantly with the duration of intensive care stay. Patients who developed IAH/ACS had significantly higher organ failure score and greater mortality compared with those who did not. Laparotomy and drainage reduced the IAP by a median of -11 mm Hg and relieved the IAH/ACS in all patients. CONCLUSIONS: Intra-abdominal hypertension and ACS are frequent findings in patients with SAP and are associated with deterioration in organ function. Intra-abdominal pressure correlates with the severity of organ failure, and a high admission IAP is associated with prolonged intensive care stay.

The anti-inflammatory effect of glucocorticoids is mediated by glucocorticoid-induced leucine zipper in epithelial cells.

BACKGROUND: Nuclear factor kappaB (NF-kappaB) plays a key role in the pathogenesis of asthma, being linked to the production of inflammatory cytokines that drive inflammation. A recently described anti-inflammatory protein, glucocorticoid-induced leucine zipper (GILZ), interferes with NF-kappaB-mediated gene transcription in T cells and macrophages. OBJECTIVE: We sought to analyze the regulation of GILZ expression in airway epithelial cells and determine whether GILZ mediates part of the anti-inflammatory effect of corticosteroids. METHODS: GILZ expression was assessed by means of PCR and immunoblotting in human epithelial cells at baseline and after stimulation with dexamethasone or cytokines (IL-1beta, TNF-alpha, and IFN-gamma). The effect of GILZ on LPS-, IL-1beta-, and polyinosinic:polycytidylic acid-induced NF-kappaB activation was assessed in BEAS-2B cells overexpressing GILZ. The requirement for GILZ in the inhibitory action of dexamethasone was assessed by knocking down GILZ expression by means of small interfering RNA (siRNA) technology. RESULTS: GILZ is constitutively expressed by human airway epithelial cells, and its levels are increased by dexamethasone and decreased by inflammatory cytokines. Overexpression of GILZ in BEAS-2B cells significantly inhibited the ability of IL-1beta, LPS, and polyinosinic:polycytidylic acid to activate NF-kappaB, whereas knockdown of GILZ inhibited the ability of dexamethasone to suppress IL-1beta-induced chemokine expression. CONCLUSION: This study demonstrates the expression of GILZ in human airway epithelial cells, its induction by dexamethasone, its suppression by inflammatory cytokines, and its role in mediating the anti-inflammatory effects of dexamethasone. CLINICAL IMPLICATIONS: Therapeutic upregulation of GILZ may be a novel strategy for the treatment of asthma.

The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database.

INTRODUCTION: To evaluate the impact of recent evidence-based treatments for severe sepsis in routine clinical care requires an understanding of the underlying epidemiology, particularly with regard to trends over time. We interrogated a high quality clinical database to examine trends in the incidence and mortality of severe sepsis over a nine-year period. METHODS: Admissions with severe sepsis occurring at any time within 24 hours of admission to critical care were identified to an established methodology using raw physiological data from the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, containing data from 343,860 admissions to 172 adult, general critical care units in England, Wales and Northern Ireland between December 1995 and January 2005. Generalised linear models were used to assess changes in the incidence, case mix, outcomes and activity of these admissions. RESULTS: In total, 92,672 admissions (27.0%) were identified as having severe sepsis in the first 24 hours following admission. The percentage of admissions with severe sepsis during the first 24 hours rose from 23.5% in 1996 to 28.7% in 2004. This represents an increase from an estimated 18,500 to 31,000 admissions to all 240 adult, general critical care units in England, Wales and Northern Ireland. Hospital mortality for admissions with severe sepsis decreased from 48.3% in 1996 to 44.7% in 2004, but the total number of deaths increased from an estimated 9,000 to 14,000. The treated incidence of severe sepsis per 100,000 population rose from 46 in 1996 to 66 in 2003, with the associated number of hospital deaths per 100,000 population rising from 23 to 30. CONCLUSION: The population incidence of critical care admission with severe sepsis during the first 24 hours and associated hospital deaths are increasing. These baseline data provide essential information to those wishing to evaluate the introduction of the Surviving Sepsis Campaign care bundles in UK hospitals.

Returning home after intensive care: a comparison of symptoms of anxiety and depression in ICU and elective cardiac surgery patients and their relatives.

OBJECTIVE: This study gathered data on symptoms of anxiety and depression in patients and relatives after discharge from intensive care and examined whether the intensive care population differ from an elective cardiac surgery group with regards to their anxiety and depression symptom reporting. DESIGN AND SETTING: A single measurement point matched group comparison study in an ICU follow-up programme. PATIENTS AND PARTICIPANTS: Twenty ICU patients and their relatives and a matched comparison group of 15 elective cardiac surgery patients and their relatives. MEASUREMENTS AND RESULTS: Patients and relatives completed the Hospital Anxiety and Depression Scale. Relatives answered an open question to explore the perceived impact of Intensive care/cardiac surgery on their lives. ICU patients' relatives reported significantly higher number of symptoms of anxiety than did ICU patients, higher number of symptoms of depression than cardiac surgery patients' relatives, and more troubling and life-altering experiences than the relatives of cardiac surgery patients. CONCLUSIONS: Relatives of ICU patients also suffer anxiety and depression, and services should address this need. Group differences suggest that ICU patients' relatives have "unique" characteristics of depression symptom reporting.

The low molecular weight GTPase RhoA and atypical protein kinase Czeta are required for TLR2-mediated gene transcription.

The Rho GTPases are molecular switches that regulate many essential cellular processes, including actin dynamics, gene transcription, cell cycle progression, cell adhesion, and motility. In this study, we report that stimulation of TLR2 in human epithelial and monocytic cells leads to rapid and transient activation of RhoA. RhoA cooperated with the canonical I-kappaB kinase-mediated pathway that induces the release of NF-kappaB, in regulating the trans activation of the NF-kappaB subunit p65/RelA by affecting Ser(311) phosphorylation, and subsequent cytokine production. Another consequence of TLR2 stimulation by bacterial derived products was the activation of atypical protein kinase C (PKC) zeta and association of this protein kinase with RhoA. Inhibition of PKCzeta decreased NF-kappaB activation and p65/RelA trans activation without affecting I-kappaBalpha degradation. The observation of a transient, stimulus-dependent association of RhoA with PKCzeta suggests that RhoA mediates at least partially its effect on gene transcription through atypical PKC. In contrast to previous studies, identifying Rac1-PI3K as an upstream element in TLR2-initiated response to NF-kappaB, PI3K signaling was not required for RhoA or PKCzeta activity. These results indicate that multiple GTPase-regulated pathways emerge from stimulated Toll receptors, controlling different aspects of NF-kappaB-mediated gene transcription.

Post-traumatic stress disorder-related symptoms in relatives of patients following intensive care.

OBJECTIVE: To evaluate the effectiveness of the provision of information in the form of a rehabilitation program following critical illness in reducing psychological distress in the patients' close family. DESIGN: Randomised controlled trial, blind at follow-up with final assessment at 6 months. SETTING: Two district general hospitals and one teaching hospital. PATIENTS AND PARTICIPANTS: The closest family member of 104 recovering intensive care unit (ICU) patients. INTERVENTIONS: Ward visits, ICU clinic appointments at 2 and 6 months. Relatives and patients received the rehabilitation program at 1 week after ICU discharge. The program comprised a 6-week self-help manual containing information about recovery from ICU, psychological information and practical advice. MEASUREMENTS AND RESULTS: Psychological recovery of relatives was assessed by examining the rate of depression, anxiety, and post-traumatic stress disorder (PTSD)-related symptoms by 6 months after ICU. The proportion of relatives scoring in the range >19 on the Impact of Events Scale (cause for concern) was high in both groups at 49% at 6 months. No difference was shown in the rate of depression, anxiety, or PTSD-related symptoms between the study groups. CONCLUSION: A high incidence of psychological distress was evident in relatives. Written information concerning recovery from ICU provided to the patient and their close family did not reduce this. High levels of psychological distress in patients were found to be correlated with high levels in relatives.

Rehabilitation after critical illness: a randomized, controlled trial.

OBJECTIVE: To evaluate the effectiveness of a rehabilitation program following critical illness to aid physical and psychological recovery. DESIGN: Randomized controlled trial, blind at follow-up with final assessment at 6 months. SETTING: Two district general hospitals and one teaching hospital. PATIENTS: Patients were 126 consecutively admitted intensive care patients meeting the inclusion criteria. INTERVENTIONS: Control patients received ward visits, three telephone calls at home, and clinic appointments at 8 wks and 6 months. Intervention patients received the same plus a 6-wk self-help rehabilitation manual. MEASUREMENTS AND MAIN RESULTS: We measured levels of depression and anxiety (Hospital Anxiety and Depression Scale), phobic symptoms (Fear Index), posttraumatic stress disorder (PTSD)-related symptoms (Impact of Events Scale), and scores on the Short-Form Health Survey physical dimension 8 wks and 6 months after intensive care unit (ICU) treatment. Memory for ICU was assessed at 2 wks post-ICU discharge using the ICU Memory Tool.The intervention group improved, compared with the control patients, on the Short-Form Health Survey physical function scores at 8 wks and 6 months (p =.006), and there was a trend to a lower rate of depression at 8 wks (12% vs. 25%). However, there were no differences in levels of anxiety and PTSD-related symptoms between the groups. The presence of delusional memories was correlated significantly with both anxiety and Impact of Events Scale scores. CONCLUSIONS: A self-help rehabilitation manual is effective in aiding physical recovery and reducing depression. However, in those patients recalling delusional memories from the ICU, further psychological care may be needed to reduce the incidence of anxiety and PTSD-related symptoms.