Multi-chamber parenteral nutrition (PN) bags are safe and cost-effective in replacing compounded PN regimens in hospitalised patients.

BACKGROUND & AIMS: There is varied international practice in the use of ready-made multi-chamber bags (MCBs) and compounded parenteral nutrition (PN). Recent national aseptic pharmacy capacity limitations have restricted compounded PN production so we aimed to explore outcomes associated with the increased use of MCB vs compounded regimens during a period of change in PN supplies. METHODS: This was a point prevalence study conducted over two time periods, Period 1: 01.01.2022-31.03.2022 and Period 2: 01.10.2022-31.12.2022. Data were collected on PN regimen, outcomes, cost and aseptic time required to prepare PN bags. RESULTS: 263 patients were included: 132 in Period 1 and 131 in Period 2. Overall, 2263 PN bags were utilised; 1179 in Period 1 and 1084 in Period 2. In Period 1, of all utilised bags, 138 (11.7%) were compounded PN, 356 (30.2%) supplemented MCBs and 685 (58.1%) manipulated MCBs whereas in Period 2, 0 were compounded PN, 546 (50.3%) supplemented MCBs and 538 (49.6%) manipulated MCBs. There were no significant differences in the proportion of patients with deranged blood tests between the study periods. In both periods there were only two episodes of catheter-related blood stream infection. The total cost saved in Period 2 compared to Period 1 was £20,684 and total aseptic staff time saved was 191 h. CONCLUSION: Wider use of in-hospital MCB PN regimens could lead to a reduction in the need for compounded PN produced by aseptic pharmacy facilities, saving costs while maintaining good patient outcomes.

Association between chronic intestinal failure etiology and eGFR trajectory in adults receiving home parenteral nutrition: A retrospective longitudinal cohort study.

BACKGROUND: Patients with chronic intestinal failure (CIF) are at increased risk of developing renal impairment. The aim of this study was to evaluate the occurrence of chronic kidney disease (CKD) in patients dependent on home parenteral nutrition (HPN) and assess risk factors for renal impairment, including patients with all mechanisms of CIF. METHODS: This was a cohort study of patients initiated on HPN between March 1, 2015, and March 1, 2020, at a national UK IF Reference Centre. Patients were followed from their first discharge with HPN until HPN cessation or the end of follow-up on December 31, 2021. RESULTS: There were 357 patients included in the analysis. Median follow-up time was 4.7 years. At baseline, >40% of patients had renal impairment, with 15.4% fulfilling the criteria for CKD. Mean estimated glomerular filtration rate (eGFR) decreased significantly during the first year after initiation of HPN from 93.32 ml/min/1.73 m2 to 86.30 ml/min/1.73 m2 at the first year of follow-up (P = 0.002), with sequential stabilization of renal function. Increased age at HPN initiation and renal impairment at baseline were associated with decreased eGFR. By the end of follow-up, 6.7% patients developed renal calculi and 26.1% fulfilled the criteria for CKD. CONCLUSION: This is the largest study of renal function in patients receiving long-term HPN. After the first year following HPN initiation, the rate of decline in eGFR was similar to that expected in the general population. These findings should reassure patients and clinicians that close monitoring of renal function can lead to good outcomes.

Long-term survival following fungal catheter-related bloodstream infection for patients with intestinal failure receiving home parenteral support.

BACKGROUND: A fungal-related catheter-related bloodstream infection (CRBSI) is less frequent than those induced by bacteria. In the past, a single episode of fungal CRBSI has been used as a marker of home parenteral nutrition (HPN) failure and thus a possible indication for intestinal transplantation. METHODS: Survival outcomes were assessed from a prospectively maintained database of patients initiated on HPN for underlying chronic intestinal failure between 1993 and 2018, with a censoring date of December 31, 2020. Cox regression was performed to assess predictors of mortality with univariable and multivariable analysis. RESULTS: A total of 1008 patients were included in the study, with a total of 1 364 595 catheter days. There were 513 CRBSI events recorded in 262 patients, equating to a CRBSI rate of 0.38/1000 catheter days. A total of 38/262 (14.5%) patients had at least one episode of fungal CRBSI, whereas 216/262 (82.4%) had at least one bacterial but no fungal CRBSI. The median time between HPN initiation and the first CRBSI episode was 20.6 months (95% confidence interval, 16.5-24.1). Episodes of fungal or bacterial CRBSI and the number of CRBSI episodes were not associated with increased mortality. Overall, 15 CRBSI-related deaths were observed in the observation period (0.01 CRBSI deaths/1000 catheter days), two of these were fungal in origin. CONCLUSION: The occurrence of a fungal CRBSI does not increase the risk of death compared with patients who have bacterial CRBSI or those without a CRBSI event.

Barrett's oesophagus with indefinite for dysplasia shows high rates of prevalent and incident neoplasia in a UK multicentre cohort.

AIMS: Barrett's oesophagus with indefinite for dysplasia (IDD) carries a risk of prevalent and incident dysplasia and oesophageal adenocarcinoma. This study seeks to determine the risk of neoplasia in a multicentre prospective IDD cohort, along with determining adherence to British Society of Gastroenterology (BSG) guidelines for management and histology reporting. METHODS: This was a cohort study using prospectively collected data from pathology databases from two centres in the North West of England (UK). Cases with IDD were identified over a 10-year period. Data were obtained on patient demographics, Barrett's endoscopy findings and histology, outcomes and histological reporting. RESULTS: 102 biopsies with IDD diagnosis in 88 patients were identified. Endoscopy was repeated in 78/88 (88%) patients. 12/78 progressed to low-grade dysplasia (15% or 2.6 per 100 person years), 6/78 (7.7%, 1.3 per 100 person years) progressed to high-grade dysplasia and 6/78 (7.7%, 1.3 per 100 person years) progressed to oesophageal adenocarcinoma. The overall incidence rate for progression to any type of dysplasia was 5.1 per 100 person years. Cox regression analysis identified longer Barrett's segment, multifocal and persistent IDD as predictors of progression to dysplasia. Histology reporting did not meet 100% adherence to the BSG histology reporting minimum dataset prior to or after the introduction of the guidelines. CONCLUSIONS: IDD carries significant risk of progression to dysplasia or neoplasia. Therefore, careful diagnosis and management aided by clear histological reporting of these cases is required to diagnose prevalent and incident neoplasia.

Disease Recurrence and Long-term Outcomes Following the Development of Intestinal Failure in Crohn's Disease: Over 20 Years of Experience from a National Reference Centre.

BACKGROUND AND AIMS: Intestinal failure [IF] is a recognised complication of Crohn's disease [CD]. The aim of this study was to identify factors predicting the development and recurrence of CD in patients with IF [CD-IF], and their long-term outcomes. METHODS: This was a cohort study of adults with CD-IF admitted to a national UK IF reference centre between 2000 and 2021. Patients were followed from discharge with home parenteral nutrition [HPN] until death or February 28, 2021. RESULTS: In all, 124 patients were included; 47 [37.9%] changed disease location and 55 [44.4%] changed disease behaviour between CD and CD-IF diagnosis, with increased upper gastrointestinal involvement [4.0% vs 22.6% patients], p <0.001. Following IF diagnosis, 29/124 [23.4%] patients commenced CD prophylactic medical therapy; 18 [62.1%] had a history of stricturing or penetrating small bowel disease; and nine [31.0%] had ileocolonic phenotype brought back into continuity. The cumulative incidence of disease recurrence was 2.4% at 1 year, 16.3% at 5 years and 27.2% at 10 years; colon-in-continuity and prophylactic treatment were associated with an increased likelihood of disease recurrence. Catheter-related bloodstream infection [CRBSI] rate was 0.32 episodes/1000 catheter days, with no association between medical therapy and CRBSI rate. CONCLUSIONS: This is the largest series reporting disease behaviour and long-term outcomes in CD-IF and the first describing prophylactic therapy use. The incidence of disease recurrence was low. Immunosuppressive therapy appears to be safe in HPN-dependent patients with no increased risk of CRBSI. The management of CD-IF needs to be tailored to the patient's surgical disease history alongside disease phenotype.

Body composition in patients with type 2 intestinal failure.

BACKGROUND: Measurement of body composition is a valuable clinical tool for nutrition assessments, but there are no data on the merits of assessment modalities in type 2 intestinal failure (IF). The aim of this study was to evaluate the prevalence of low muscle mass and quality in type 2 IF, comparing bioelectric impedance analysis (BIA) and computed tomography (CT) at the third lumbar vertebra level. METHODS: Patients admitted with acute severe (type 2) IF to a national UK IF center who had BIA measurement and CT scan as part of routine care within 40 days of anthropometric measurement were included in this cross-sectional study. Data were also collected on patient demographics and clinical characteristics. RESULTS: Forty-four patients meeting inclusion criteria were included. Low muscle mass was detected in 37 out of 44 (84.1%) patients by CT scan and in 30 of out 44 (68.2%) by BIA. Low muscle quality was detected in 22 out of 44 (50%) patients by CT scan and in 40 out of 44 (90.1%) by BIA. Comparison of CT and BIA measurements showed a moderate correlation of muscle, Spearman ρ 0.65 (95% CI, 0.42-0.81; P < 0.001), and a strong correlation of body fat mass measurements, Spearman ρ 0.79 (95% CI, 0.62-0.89; P < 0.001). CONCLUSION: This is the first study to demonstrate that low muscle mass is common in patients with type 2 IF, regardless of body composition assessment modality. A larger cohort study is required to validate the impact of low muscle mass and quality on clinical outcomes and the role of targeted interventions to improve the care of patients with type 2 IF.

Standardised survival and excess Life Years Lost in patients with type 3 intestinal failure.

BACKGROUND & AIMS: Long term outcomes have been reported in home parenteral nutrition (HPN)-dependent patients with type 3 intestinal failure (IF), but there are limited survival data standardised to the general population that would help provide a meaningful prognosis for patients and clinicians. The primary aim of this study was therefore to investigate the survival of HPN-dependent patients and to evaluate the specific impact of type 3 IF on their life expectancy standardised to that of the general population. METHODS: This was a cohort study of adult patients initiated on HPN between 1978 and 2018 at a national UK IF reference centre and followed up until death or censoring date of 31st December 2020. The standardised mortality ratio (SMR) was calculated as observed deaths divided by expected deaths using UK Office for National Statistics database. Excess Life Years Lost (LYL) were calculated separately for each sex as the differences in average life expectancy between patients with type 3 IF and the general population. Survival data were evaluated using cox regression models adjusting for confounding. RESULTS: In total, 1046 patients were identified, with a total observation time of 7344.1 patient-years. Patients with malignancy (n = 206) were excluded from the survival analysis. Of the remaining 840 patients, 398 were alive by the end of follow-up. The probability of survival was 91.8% at 1 year, 69.3% at 5 years, 54.3% at 10 years, 29.8% at 20 years and 16.7% at 30 years. Patients who did not achieve nutritional autonomy had an increased likelihood of death compared to patients who ceased HPN. In total, 40 (9.0%) deaths were HPN or IF-related, while underlying disease leading to IF accounted for 98 (22.2%) deaths. There were 270 (61.1%) deaths not related to IF, with the majority of these patients dying from infections unrelated to HPN. Overall mortality rates were higher among patients with a diagnosis of type 3 IF compared with the general UK population with a SMR of 7.48 (95% CI 6.80 to 8.21) and an excess mortality rate of 54.0 per 1000 person-years. All mechanisms of IF were associated with excess mortality, with SMR ranging from 6.82 (95% CI 5.98 to 7.72) for short bowel syndrome to 15.51 (95% CI 11.73 to 20.03) for dysmotility. On average, the excess LYL was 17.45 years for males and 17.39 years for females compared with the general population of the same age. CONCLUSION: This the largest single-centre series reporting survival outcomes in patients with type 3 IF over more than a four-decade period and the first to report LYL in this patient cohort. Type 3 IF was associated with more than seven-fold higher mortality rates than for the general UK population and shorter life expectancies of more than 17 years. Survival, however, was better in those able to achieve nutritional autonomy. Since the majority of deaths were due to non-HPN or non-IF causes, there is clearly a need now to further explore these causes of death in order to improve our understanding of excessive mortality in type 3 IF and develop ways to prevent it.

Hybrid model of compounded and multichamber bag parenteral nutrition for adults with chronic intestinal failure.

BACKGROUND: Although international guidelines support the use of commercially available multichamber bags (MCBs), the majority of home parenteral nutrition (HPN) in the United Kingdom has been compounded PN, tailored to the patient. However, national capacity limitations in aseptic facilities have necessitated the increased use of MCBs. There are no studies evaluating the appropriateness or benefits of using a "hybrid" regimen incorporating both MCBs and compounded PN in patients already established on compounded HPN. METHODS: This was a cross-sectional audit evaluation conducted on September 1, 2021, at a national United Kingdom reference center. All HPN-dependent adults prescribed HPN for chronic intestinal failure were assessed by a multidisciplinary team for their potential of being switched to a "hybrid" regimen of MCBs and compounded PN. RESULTS: Of 180 patients currently receiving compounded HPN that included intravenous nitrogen with glucose ± lipid, 65 (36.1%) were deemed clinically suitable for a hybrid PN regimen, with minimal variance in PN constituents per week (volume 0%, non-nitrogen kilocalories 0%, nitrogen 0%, fat -0.2%, glucose 0%, sodium 0%, potassium 0%, calcium 0%, magnesium 0%, and phosphate -0.1%) and requiring no additional central venous catheter manipulations. The potential reduction in compounded PN would reduce by 3627 bags per year, equating to a cost saving of £141,453 per year (equivalent to $178,885). CONCLUSION: Wider use of hybrid MCB/compounded HPN regimens could lead to a reduction in the need for compounded PN to be produced by aseptic facilities. Further evaluation of acceptability and tolerance of hybrid regimens by patients already receiving compounded HPN is required.

Long-Term Outcomes in Patients with Intestinal Failure Due to Short Bowel Syndrome and Intestinal Fistula.

Short bowel syndrome (SBS) and enterocutaneous or enteroatmospheric fistulas are common indications for home parenteral nutrition (HPN). However, there are few data describing factors influencing surgical decision-making or outcomes particularly following fistula development. We aimed to compare outcomes between patients with SBS and fistulas and explore surgical decision-making. HPN-dependent adults from 2001−2018 at a national reference centre were included in this study. HPN cessation was analysed using death as competing risk. In total, 465 patients (SBS (62%), fistula (38%)) were included, with median HPN dependency of 2.6 years. In total, 203 patients underwent reconstructive surgery; while frailty was the commonest reason for not undergoing surgery (49.2%), 22.7% declined surgery. Overall, 170 ceased HPN, with a probability of 13.8%, 34.1% and 38.3% at 1, 5 and 10 years, respectively. Patients undergoing surgery had higher nutritional autonomy rates (109.8 incidences/1000 patient years) compared to those not undergoing surgery (18.1 incidences/1000 patient years; p < 0.001). A total of 295 patients (63.4%) were predicted to cease HPN based on gastrointestinal anatomy but only 162/295 (54.9%) achieved this; those unable to do so were older with a higher comorbidity index. There were no differences in long-term nutritional and survival outcomes or surgical decisions between patients with SBS and fistulas, or between enterocutaneous and enteroatmospheric fistulas. This study represents one of the largest datasets describing the ability of HPN-dependent patients with SBS or fistulas to achieve nutritional autonomy. While reconstructive surgery facilitates HPN cessation, approximately one-fifth of patients declined surgery despite HPN dependency. These data will better inform patient expectation and help plan alternative therapies.

Home Parenteral Nutrition in Patients with Advanced Cancer: Quality Outcomes from a Centralized Model of Care Delivery.

Lack of expertise in home parenteral nutrition (HPN) management has been reported as a barrier to its initiation in patients with advanced cancer (AC), and there are limited data describing hospital readmissions and HPN-related complications. We aimed to assess a centralized approach for managing HPN in AC and evaluate associated outcomes, including hospital readmissions and HPN-related complications. This was a cohort study of adults with AC requiring palliative HPN between 2010-2018 at a tertiary intestinal failure (IF) center, primarily utilizing a centralized model of HPN oversight to discharge patients remotely from an oncology center to their homes over a wide geographic area. A total of 126 patients were included, with a median distance between the patient's home and the IF center of 17.5 km (IQR 10.9-39.1; maximum 317.4 km). A total of 28 (22%) patients experienced at least one HPN-related complication, the most common being a central venous catheter (CVC) occlusion and electrolyte abnormalities. The catheter-related bloodstream infection (CRBSI) rate was 0.49/1000 catheter days. The CVC type, administration of concomitant chemotherapy via a distinct CVC lumen separate from PN, venting gastrostomy and distance between the patient's home and the IF center were not associated with CRBSI or mechanical CVC complications. A total of 82 (65.1%) patients were readmitted while on HPN, but only 7 (8.5%) of these readmissions were HPN-related. A total of 44 (34.9%) patients died at home, 41 (32.5%) at a hospice and 41 (32.5%) in a hospital. In conclusion, this study demonstrates that a centralized approach to IF care can provide HPN to patients over a large geographical area while maintaining low HPN-related complications that are comparable to patients requiring HPN for benign conditions and low hospital readmission rates.

Sepsis outcomes in patients with pre-existing liver disease.

Aim of the study: To determine the characteristics, including the use of various diagnostic criteria, outcomes and treatment strategies in septic patients treated outside of the critical care area with pre-existing liver disease (LD). Material and methods: The study population included patients recruited into two annual 24-hour prospective point-prevalence studies on the general wards and emergency departments across all Welsh acute hospitals in 2016 and 2017. Data were collected on patient demographics, observations and SIRS, SOFA and qSOFA scores. Results: Out of 839 recruited patients, 24 (2.9%) had a past medical history of LD. 12/24 (50%) had a SIRS score ≥ 2, 21/24 (87.5%) a SOFA score ≥ 2 and 3/24 (12.5%) a qSOFA score ≥ 2. Patients with LD had 2.4 times higher odds (95% CI = 1.07-5.53, p = 0.03) of mortality after the sepsis episode. LD patients were younger than non-LD patients (p = 0.04) but not significantly different in frailty, do not attempt cardiopulmonary resuscitation (DNA-CPR) status or ceiling of care (p = 0.78, p = 0.54, p = 0.06, respectively). Conclusions: The 90-day mortality was greater in patients with LD than the rest of the population. Management of sepsis in LD patients poses a challenge with current therapeutic bundles being underused and of unclear significance in improving patient outcome.

The Use of Different Sepsis Risk Stratification Tools on the Wards and in Emergency Departments Uncovers Different Mortality Risks: Results of the Three Welsh National Multicenter Point-Prevalence Studies.

OBJECTIVES: To compare the performance of Sequential Organ Failure Assessment, systemic inflammatory response syndrome, Red Flag Sepsis, and National Institute of Clinical Excellence sepsis risk stratification tools in the identification of patients at greatest risk of mortality from sepsis in nonintensive care environments. DESIGN: Secondary analysis of three annual 24-hour point-prevalence study periods. SETTING: The general wards and emergency departments of 14 acute hospitals across Wales. Studies were conducted on the third Wednesday of October in 2017, 2018, and 2019. PATIENTS: We screened all patients presenting to the emergency department and on the general wards. MEASUREMENTS AND MAIN RESULTS: We recruited 1,271 patients, of which 724 (56.9%) had systemic inflammatory response syndrome greater than or equal to 2, 679 (53.4%) had Sequential Organ Failure Assessment greater than or equal to 2, and 977 (76.9%) had Red Flag Sepsis. When stratified according to National Institute of Clinical Excellence guidelines, 450 patients (35.4%) were in the "High risk" category in comparison with 665 (52.3%) in "Moderate to High risk" and 156 (12.3%) in "Low risk" category. In a planned sensitivity analysis, we found that none of the tools accurately predicted mortality at 90 days, and Sequential Organ Failure Assessment and National Institute of Clinical Excellence tools showed only moderate discriminatory power for mortality at 7 and 14 days. Furthermore, we could not find any significant correlation with any of the tools at any of the mortality time points. CONCLUSIONS: Our data suggest that the sepsis risk stratification tools currently utilized in emergency departments and on the general wards do not predict mortality adequately. This is illustrated by the disparity in mortality risk of the populations captured by each instrument, as well as the weak concordance between them. We propose that future studies on the development of sepsis identification tools should focus on identifying predicator values of both the short- and long-term outcomes of sepsis.

Four consecutive yearly point-prevalence studies in Wales indicate lack of improvement in sepsis care on the wards.

The 'Sepsis Six' bundle was promoted as a deliverable tool outside of the critical care settings, but there is very little data available on the progress and change of sepsis care outside the critical care environment in the UK. Our aim was to compare the yearly prevalence, outcome and the Sepsis Six bundle compliance in patients at risk of mortality from sepsis in non-intensive care environments. Patients with a National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled into four yearly 24-h point prevalence studies, carried out in fourteen hospitals across Wales from 2016 to 2019. We followed up patients to 30 days between 2016-2019 and to 90 days between 2017 and 2019. Out of the 26,947 patients screened 1651 fulfilled inclusion criteria and were recruited. The full 'Sepsis Six' care bundle was completed on 223 (14.0%) occasions, with no significant difference between the years. On 190 (11.5%) occasions none of the bundle elements were completed. There was no significant correlation between bundle element compliance, NEWS or year of study. One hundred and seventy (10.7%) patients were seen by critical care outreach; the 'Sepsis Six' bundle was completed significantly more often in this group (54/170, 32.0%) than for patients who were not reviewed by critical care outreach (168/1385, 11.6%; p < 0.0001). Overall survival to 30 days was 81.7% (1349/1651), with a mean survival time of 26.5 days (95% CI 26.1-26.9) with no difference between each year of study. 90-day survival for years 2017-2019 was 74.7% (949/1271), with no difference between the years. In multivariate regression we identified older age, heart failure, recent chemotherapy, higher frailty score and do not attempt cardiopulmonary resuscitation orders as significantly associated with increased 30-day mortality. Our data suggests that despite efforts to increase sepsis awareness within the NHS, there is poor compliance with the sepsis care bundles and no change in the high mortality over the study period. Further research is needed to determine which time-sensitive ward-based interventions can reduce mortality in patients with sepsis and how can these results be embedded to routine clinical practice.Trial registration Defining Sepsis on the Wards ISRCTN 86502304 https://doi.org/10.1186/ISRCTN86502304 prospectively registered 09/05/2016.

Prevalence and Outcomes of Acute Hypoxaemic Respiratory Failure in Wales: The PANDORA-WALES Study.

BACKGROUND: We aimed to identify the prevalence of acute hypoxaemic respiratory failure (AHRF) in the intensive care unit (ICU) and its associated mortality. The secondary aim was to describe ventilatory management as well as the use of rescue therapies. METHODS: Multi-centre prospective study in nine hospitals in Wales, UK, over 2-month periods. All patients admitted to an ICU were screened for AHRF and followed-up until discharge from the ICU. Data were collected from patient charts on patient demographics, clinical characteristics, management and outcomes. RESULTS: Out of 2215 critical care admissions, 886 patients received mechanical ventilation. A total of 197 patients met inclusion criteria and were recruited. Seventy (35.5%) were non-survivors. Non-survivors were significantly older, had higher SOFA scores and received more vasopressor support than survivors. Twenty-five (12.7%) patients who fulfilled the Berlin definition of acute respiratory distress syndrome (ARDS) during the ICU stay without impact on overall survival. Rescue therapies were rarely used. Analysis of ventilation showed that median Vt was 7.1 mL/kg PBW (IQR 5.9-9.1) and 21.3% of patients had optimal ventilation during their ICU stay. CONCLUSIONS: One in four mechanically ventilated patients have AHRF. Despite advances of care and better, but not optimal, utilisation of low tidal volume ventilation, mortality remains high.

Assessment of technical parameters and skills training to inform a simulation-based training program for semi-automated robotic colonoscopy.

Background and study aims Video-colonoscopy, despite being the gold-standard for diagnosis of colorectal lesions, has limitations including patient discomfort and risk of complications. This study assessed training characteristics and acceptability in operators of a new robotic colonoscope (RC). Materials and methods Participants (n = 9) with varying degrees of skill and background knowledge in colonoscopy performed colonoscopies with a RC on a simulation-based training model. Quantitative procedure-related and qualitative operator-related parameters were recorded. Results Polyp detection rate was highest in the novice group (91.67 %) followed by experts (86.11 %), then equally, trainees and video gamers (79.17 %). Four participants repeated the procedure at a follow-up session. Each participant improved cecal intubation time and had the same or higher polyp detection rate. The potential role for RC was identified for an out-of-hospital environment and as a novel diagnostic tool. Conclusions Results from this pilot suggest that operators at all skill levels found the RC acceptable and potentially useful as a diagnostic tool. Acquisition of skills with RC seems to improve rapidly to a clinically relevant level with simulation-based training.

Complement system biomarkers in first episode psychosis.

Several lines of evidence implicate immunological/inflammatory factors in development of schizophrenia. Complement is a key driver of inflammation, and complement dysregulation causes pathology in many diseases. Here we explored whether complement dysregulation occurred in first episode psychosis (FEP) and whether this provides a source of biomarkers. Eleven complement analytes (C1q, C3, C4, C5, factor B [FB], terminal complement complex [TCC], factor H [FH], FH-related proteins [FHR125], Properdin, C1 inhibitor [C1inh], soluble complement receptor 1 [CR1]) plus C-reactive protein (CRP) were measured in serum from 136 first episode psychosis (FEP) cases and 42 mentally healthy controls using established in-house or commercial ELISA. The relationship between caseness and variables (analytes measured, sex, age, ethnicity, tobacco/cannabis smoking) was tested by multivariate logistic regression. When measured individually, only TCC was significantly different between FEP and controls (p=0.01). Stepwise selection demonstrated interdependence between some variables and revealed other variables that significantly and independently contributed to distinguishing cases and controls. The final model included demographics (sex, ethnicity, age, tobacco smoking) and a subset of analytes (C3, C4, C5, TCC, C1inh, FHR125, CR1). A receiver operating curve analysis combining these variables yielded an area under the curve of 0.79 for differentiating FEP from controls. This model was confirmed by multiple replications using randomly selected sample subsets. The data suggest that complement dysregulation occurs in FEP, supporting an underlying immune/inflammatory component to the disorder. Classification of FEP cases according to biological variables rather than symptoms would help stratify cases to identify those that might most benefit from therapeutic modification of the inflammatory response.

Real World Patterns of Antimicrobial Use and Microbiology Investigations in Patients with Sepsis outside the Critical Care Unit: Secondary Analysis of Three Nation-Wide Point Prevalence Studies.

Recent description of the microbiology of sepsis on the wards or information on the real-life antibiotic choices used in sepsis is lacking. There is growing concern of the indiscriminate use of antibiotics and omission of microbiological investigations in the management of septic patients. We performed a secondary analysis of three annual 24-h point-prevalence studies on the general wards across all Welsh acute hospitals in years 2016-2018. Data were collected on patient demographics, as well as radiological, laboratory and microbiological data within 48-h of the study. We screened 19,453 patients over the three 24 h study periods and recruited 1252 patients who fulfilled the entry criteria. 775 (64.9%) patients were treated with intravenous antibiotics. Only in 33.65% (421/1252) of all recruited patients did healthcare providers obtain blood cultures; in 25.64% (321/1252) urine cultures; in 8.63% (108/1252) sputum cultures; in 6.79% (85/1252) wound cultures; in 15.25% (191/1252) other cultures. Out of the recruited patients, 59.1% (740/1252) fulfilled SEPSIS-3 criteria. Patients with SEPSIS-3 criteria were significantly more likely to receive antibiotics than the non-septic cohort (p < 0.0001). In a multivariable regression analysis increase in SOFA score, increased number of SIRS criteria and the use of the official sepsis screening tool were associated with antibiotic administration, however obtaining microbiology cultures was not. Our study shows that antibiotics prescription practice is not accompanied by microbiological investigations. A significant proportion of sepsis patients are still at risk of not receiving appropriate antibiotics treatment and microbiological investigations; this may be improved by a more thorough implementation of sepsis screening tools.

Complement system biomarkers in epilepsy.

PURPOSE: To explore whether complement dysregulation occurs in a routinely recruited clinical cohort of epilepsy patients, and whether complement biomarkers have potential to be used as markers of disease severity and seizure control. METHODS: Plasma samples from 157 epilepsy cases (106 with focal seizures, 46 generalised seizures, 5 unclassified) and 54 controls were analysed. Concentrations of 10 complement analytes (C1q, C3, C4, factor B [FB], terminal complement complex [TCC], iC3b, factor H [FH], Clusterin [Clu], Properdin, C1 Inhibitor [C1Inh] plus C-reactive protein [CRP]) were measured using enzyme linked immunosorbent assay (ELISA). Univariate and multivariate statistical analysis were used to test whether combinations of complement analytes were predictive of epilepsy diagnoses and seizure occurrence. Correlation between number and type of anti-epileptic drugs (AED) and complement analytes was also performed. RESULTS: We found: CONCLUSION: This study adds to evidence implicating complement in pathogenesis of epilepsy and may allow the development of better therapeutics and prognostic markers in the future. Replication in a larger sample set is needed to validate the findings of the study.

Red-flag sepsis and SOFA identifies different patient population at risk of sepsis-related deaths on the general ward.

Controversy exists regarding the best diagnostic and screening tool for sepsis outside the intensive care unit (ICU). Sequential organ failure assessment (SOFA) score has been shown to be superior to systemic inflammatory response syndrome (SIRS) criteria, however, the performance of "Red Flag sepsis criteria" has not been tested formally.The aim of the study was to investigate the ability of Red Flag sepsis criteria to identify the patients at high risk of sepsis-related death in comparison to SOFA based sepsis criteria. We also investigated the comparison of Red Flag sepsis to quick SOFA (qSOFA), SIRS, and national early warning score (NEWS) scores and factors influencing patient mortality.Patients were recruited into a 24-hour point-prevalence study on the general wards and emergency departments across all Welsh acute hospitals. Inclusion criteria were: clinical suspicion of infection and NEWS 3 or above in-line with established escalation criteria in Wales. Data on Red Flag sepsis and SOFA criteria was collected together with qSOFA and SIRS scores and 90-day mortality.459 patients were recruited over a 24-hour period. 246 were positive for Red Flag sepsis, mortality 33.7% (83/246); 241 for SOFA based sepsis criteria, mortality 39.4% (95/241); 54 for qSOFA, mortality 57.4% (31/54), and 268 for SIRS, mortality 33.6% (90/268). 55 patients were not picked up by any criteria. We found that older age was associated with death with OR (95% CI) of 1.03 (1.02-1.04); higher frailty score 1.24 (1.11-1.40); DNA-CPR order 1.74 (1.14-2.65); ceiling of care 1.55 (1.02-2.33); and SOFA score of 2 and above 1.69 (1.16-2.47).The different clinical tools captured different subsets of the at-risk population, with similar sensitivity. SOFA score 2 or above was independently associated with increased risk of death at 90 days. The sequalae of infection-related organ dysfunction cannot be reliably captured based on routine clinical and physiological parameters alone.

Sepsis-related deaths in the at-risk population on the wards: attributable fraction of mortality in a large point-prevalence study.

OBJECTIVE: Sepsis mortality is reported to be high worldwide, however recently the attributable fraction of mortality due to sepsis (AFsepsis) has been questioned. If improvements in treatment options are to be evaluated, it is important to know what proportion of deaths are potentially preventable or modifiable after a sepsis episode. The aim of the study was to establish the fraction of deaths directly related to the sepsis episode on the general wards and emergency departments. RESULTS: 839 patients were recruited over the two 24-h periods in 2016 and 2017. 521 patients fulfilled SEPSIS-3 criteria. 166 patients (32.4%) with sepsis and 56 patients (17.6%) without sepsis died within 90 days. Out of the 166 sepsis deaths 12 (7.2%) could have been directly related to sepsis, 28 (16.9%) possibly related and 96 (57.8%) were not related to sepsis. Overall AFsepsis was 24.1%. Upon analysis of the 40 deaths likely to be attributable to sepsis, we found that 31 patients (77.5%) had the Clinical Frailty Score ≥ 6, 28 (70%) had existing DNA-CPR order and 17 had limitations of care orders (42.5%).