Removal of common antimicrobial agents by sustained low-efficiency dialysis.

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin-tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for 8 hours during SLED (on-SLED). Arterial samples were collected every 2 hours for up to 6 hours while not receiving SLED (off-SLED) for the calculation of SLED clearance, half-life (t1/2) on-SLED and off-SLED, and the fraction of removal by SLED (fD). Twenty-one patients completed the study: 52% male, mean age (±SD) 53 ± 13 years, and mean weight of 98 ± 30 kg. Eighty-six percent had AKI, and 4 patients were receiving cefepime, 3 daptomycin, 10 meropenem, 6 piperacillin-tazobactam, and 13 vancomycin. The average SLED time was 7.3 ± 1.1 hours, and the mean ultrafiltration rate was 95 ± 52 mL/hour (range 10-211). The t1/2 on-SLED was substantially lower than the off-SLED t1/2 for all antimicrobials, and the SLED fD varied between 44% and 77%. An 8-hour SLED session led to significant elimination of most antimicrobials evaluated. If SLED is performed, modification of the dosing regimen is warranted to avoid subtherapeutic concentrations.

A randomized controlled trial of a digital cognitive-behavioral therapy program (COMPASS) for managing depression and anxiety related to living with a long-term physical health condition.

BACKGROUND: To evaluate the clinical efficacy of COMPASS, a therapist-supported digital therapeutic for reducing psychological distress (anxiety/depression) in people living with long-term physical health conditions (LTCs). METHODS: A two-armed randomized-controlled trial recruiting from LTC charities. Participants with anxiety and/or depression symptoms related to their LTC(s) were randomized (concealed allocation via independent administrator) to COMPASS (access to 11 tailored modules plus five thirty-minute therapist support sessions) or standard charity support (SCS). Assessments were completed online pre-randomization, at 6- and 12-weeks post-randomization. Primary outcome was Patient Health Questionnaire Anxiety and Depression Scale; PHQ-ADS measured at 12-weeks. Analysis used intention-to-treat principles with adjusted mean differences estimated using linear mixed-effects models. Data-analyst was blinded to group allocation. RESULTS: 194 participants were randomized to COMPASS (N = 94) or SCS (N = 100). At 12-weeks, mean level of psychological distress was 6.82 (95% confidence interval; CI 4.55-9.10) points lower (p < 0.001) in the COMPASS arm compared with SCS (standardized mean difference of 0.71 (95% CI 0.48-0.95)). The COMPASS arm also showed moderate significant treatment effects on secondary outcomes including depression, anxiety and illness-related distress and small significant effects on functioning and quality-of-life. Rates of adverse events were comparable across the arms. Deterioration in distress at 12-weeks was observed in 2.2% of the SCS arm, and no participants in the COMPASS arm. CONCLUSION: Compared with SCS, COMPASS digital therapeutic with minimal therapist input reduces psychological distress at post-treatment (12-weeks). COMPASS offers a potentially scalable implementation model for health services but its translation to these contexts needs further evaluating. TRIAL REGISTRATION: NCT04535778.

Validation of Two Scoring Tools to Predict Risk of Augmented Renal Clearance in Trauma Patients.

INTRODUCTION: Augmented renal clearance (ARC) is prevalent in trauma populations. Identification is underrecognized by calculated creatinine clearance or estimated glomerular filtration rate equations. Predictive scores may assist with ARC identification. The goal of this study was to evaluate validity of the ARCTIC score and ARC Predictor to predict ARC in critically ill trauma patients. METHODS: This single center, retrospective study was performed at an academic level 1 trauma center. Critically ill adult trauma patients undergoing 24-h urine-collection were included. Patients with serum creatinine >1.5 mg/dL, kidney replacement therapy, suspected rhabdomyolysis, chronic kidney disease, or inaccurate urine collection were excluded. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for ARCTIC Score and ARC Predictor were calculated. Receiver operating characteristic curves were created for ARCTIC score and ARC Predictor models. RESULTS: One-hundred and twenty-two patients with ARC and 78 patients without ARC were included. The ARCTIC score sensitivity, specificity, PPV, and NPV were 89%, 54%, 75%, and 75%, respectively. The ARC Predictor demonstrated sensitivity, specificity, PPV, and NPV of 77%, 88%, 91%, and 71%, respectively. Regression analyses revealed both ARCTIC score ≥6 and ARC Predictor threshold >0.5 as significant risk factors for ARC in presence of traumatic brain injury, obesity, injury severity score, and negative nitrogen balance (ARCTIC ≥6: odds ratio 8.59 [95% confidence interval 3.90-18.92], P < 0.001; ARC Predictor >0.5: odds ratio 20.07 [95% confidence interval 8.53-47.19], P < 0.001). CONCLUSIONS: These findings corroborate validity of two pragmatic prediction tools to identify patients at high risk of ARC. Future studies evaluating correlations between ARCTIC score, ARC Predictor, and clinical outcomes are warranted.

Implementing treat-to-target urate-lowering therapy during hospitalisations for gout flares.

OBJECTIVES: To evaluate a strategy designed to optimise care and increase uptake of urate-lowering therapy (ULT) during hospitalisations for gout flares. METHODS: We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment, and re-hospitalisation rates, were compared between patients hospitalised for flares in the 12 months post-implementation and a retrospective cohort of hospitalised patients from 12 months pre-implementation. RESULTS: 119 and 108 patients, respectively, were hospitalised for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n = 94 and n = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio (aOR) 11.5; 95% confidence interval (CI) 4.36-30.5; p < 0.001). After implementation, more patients achieved a serum urate ≤360 micromol/L within 6 months of discharge (10.6% pre-implementation vs. 26.8% post-implementation; aOR 3.04; 95% CI 1.36-6.78; p = 0.007). The proportion of patients re-hospitalised for flares was 14.9% pre-implementation vs. 9.3% post-implementation (aOR 0.53, 95% CI 0.22 to 1.32; p = 0.18). CONCLUSION: Over 90% of patients were initiated on ULT after implementing a strategy to optimise hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalisations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalised gout patients to achieve urate targets, closer primary-secondary care integration is still needed.

Impact of the COVID-19 pandemic on services for patients with chronic kidney disease: findings of a national survey of UK kidney centres.

BACKGROUND: Services for patients with kidney disease underwent radical adaptations in response to the COVID-19 pandemic. We undertook an online national survey of UK kidney centres to understand the nature, range, and degree of variation in these changes and to explore factors contributing to differing practice. METHODS: The survey was designed by a multidisciplinary team of kidney professionals, service users and researchers. It enquired about centre services and staffing, including psychosocial provision, and changes to these in response to the COVID-19 pandemic. Links to the survey were sent to all 68 UK kidney centres and remained active from December 2021 to April 2022, and a revised version to nurses in late 2022 for additional data. Quantitative data were analysed descriptively. Content analysis on free-text responses identified common themes. RESULTS: Analysable responses were received from 41 out of the 68 UK centres (60%), with partial data from an additional 7 (11%). Adaptations were system-wide and affected all aspects of service provision. Some changes were almost universal such as virtual consultations for outpatient appointments, with significant variation in others. Outpatient activity varied from fully maintained to suspended. Many centres reduced peritoneal dialysis access provision but in some this was increased. Centres considered that changes to transplant surgical services and for patients with advanced CKD approaching end-stage kidney disease had the greatest impact on patients. Few centres implemented adjustments aimed at vulnerable and underrepresented groups, including the frail elderly, people with language and communication needs, and those with mental health needs. Communication issues were attributed to rapid evolution of the pandemic, changing planning guidance and lack of resources. Staffing shortages, involving all staff groups particularly nurses, mainly due to COVID-19 infection and redeployment, were compounded by deficiencies in staffing establishments and high vacancy levels. Centres cited three main lessons influencing future service delivery, the need for service redesign, improvements in communication, and better support for staff. CONCLUSION: Kidney centre responses to the pandemic involved adaptations across the whole service. Though some changes were almost universal, there was wide variation in other areas. Exploring the role of centre characteristics may help planning for potential future severe service disruptions.

An Evidence-Based Theory of Psychological Adjustment to Long-Term Physical Health Conditions: Applications in Clinical Practice.

OBJECTIVE: Around 30% of people with long-term physical health conditions (LTCs) experience comorbid anxiety and depression. For many, comorbid distress is linked to difficulties adjusting to the challenges of the LTC. The aims of this article are to present a transdiagnostic theoretical model of adjustment to LTCs (TMA-LTC), demonstrate the application of this model in clinical practice, and highlight the distinguishing features of treating LTC-related distress compared with treating primary anxiety and/or depression. METHODS: A systematic review (k = 21) was conducted to collate preexisting evidence-based models of adjustment across LTCs. Models of adjustment for a range of LTCs were extracted and synthesized into a new preliminary TMA-LTC. Two expert consensus meetings were held, where experts rated the relevance and importance of all concepts within the models. RESULTS: The TMA-LTC proposes that acute critical events or ongoing illness stressors can disrupt emotional equilibrium, and that whether a person returns to equilibrium and achieves good psychological adjustment depends on a number of cognitive and behavioral factors, as well as their interpersonal, intrapersonal, environmental, and illness-specific contexts. A case study is presented to demonstrate the clinical application of this model in treating illness-related distress, highlighting how it overcomes roadblocks that may be encountered when working primarily within traditional mental health paradigms. CONCLUSIONS: As an empirically and clinically informed model, TMA-LTC provides a useful guide for assessment, formulation, and treatment in the context of psychological adjustment to LTCs. Future studies are needed to test treatments that have been developed based on TMA-LTC.

The effectiveness of cognitive behavioural therapy and third-wave cognitive behavioural interventions on diabetes-related distress: A systematic review and meta-analysis.

AIM: Diabetes-related distress is common in diabetes and has implications for well-being. Cognitive behavioural therapy (CBT) and third-wave CBT hold promise as treatments for diabetes-related distress, although previous findings are inconclusive. We aimed to conduct a systematic review with meta-analysis to understand the efficacy of these interventions in treating diabetes-related distress, while also assessing the associative benefits of these interventions on depression, anxiety and glycaemic control. We also aimed to conduct a narrative synthesis, and subgroup analyses to identify intervention components most useful in treating diabetes-related distress. METHOD: We searched seven electronic databases from inception to April 2021. Data extraction was independently performed by two reviewers. Methodological quality was assessed. The protocol was registered with the Prospective Register Of Systematic Reviews (PROSPERO): CRD42021240628. RESULTS: We included 22 randomised controlled trials investigating the efficacy of CBT and third-wave CBT interventions on diabetes-related distress. CBT for diabetes-related distress significantly reduced distress (SMD = -0.278, p = 0.010) and depression (SMD = -0.604, p = 0.016). Third-wave CBT for diabetes-related distress significantly reduced anxiety (SMD = -0.451, p = 0.034). No significant effect of either intervention on glycated haemoglobin was observed. CBT interventions that included a digital component, were delivered by a psychological practitioner, and included behavioural activation bolstered the effects on diabetes-related distress. CONCLUSIONS: CBT aiming to target diabetes-related distress is beneficial for distress and depression. Third-wave CBT for diabetes-related distress is beneficial for anxiety. More work is needed to optimise interventions to improve both mental and physical health outcomes in people with diabetes.

Gabapentinoid dosing and adverse events in patients with chronic kidney disease.

BACKGROUND: Gabapentinoids (GPs) are frequently prescribed in individuals with chronic kidney disease (CKD); however, their exclusive renal elimination warrants dose adjustments to decrease risk of toxicity. This study evaluated GP prescribing patterns and whether excessive dosing was associated with increased incidence of gabapentinoid-related adverse events (GRAEs). MATERIALS AND METHODS: A retrospective analysis of adult CKD and end-stage kidney disease (ESKD) patients hospitalized from 2014 to 2020 and receiving GPs was conducted. Patients were grouped based on whether the average daily dose prescribed was higher than recommended (inappropriately dosed, (ID)) or as recommended (appropriately dosed (AD)) for CKD stage. The occurrence of GRAEs was compared between groups. Patient characteristics, CKD stage, and hospital length of stay (LOS) were evaluated to determine association with GRAEs. RESULTS: The 200 patients included were predominantly female (51%), black (72%), CKD 5/ESKD (84%), and prescribed gabapentin (90%) with a mean age 61 ± 14 years. For the 111 (55%) patients in the AD group and 89 (45%) in the ID group there was no statistically significant difference in GRAEs (18 vs. 19%, p = 0.84). GRAEs were associated with older age (66 vs. 61 years; p < 0.001), seizure history (14% for GRAE vs. 3% for no GRAE, p = 0.02), and concomitant antipsychotic use (24% for GRAE vs. 5% for no GRAE; p < 0.001) but not with CKD severity. LOS was significantly longer for patients experiencing a GRAE (8.5 vs. 5.3 days; p < 0.001). CONCLUSION: Appropriate dosing of GPs is particularly important to minimize the risk of adverse events in patients of older age, with a history of seizures, or concomitant antipsychotic use. There is a need for prescriber education given the high frequency of inappropriate GP dosing observed in patients with advanced kidney disease.

Review of Anticoagulation in Continuous Renal Replacement Therapy.

Continuous renal replacement therapy is an important, yet challenging, treatment of critically ill patients with kidney dysfunction. Clotting within the dialysis filter or circuit leads to time off therapy and impaired delivery of prescribed treatment. Anticoagulation can be used to prevent this complication; however, doing so introduces risk for unintended complications such as bleeding or metabolic derangements in patients who are already critically ill. A thorough understanding of indications, therapeutic options, and monitoring principles is necessary for safe and effective use of this strategy. This review provides clinicians important information regarding when to anticoagulate, differences in pharmacologic agents, recommended doses, routes of drug delivery, and appropriate laboratory monitoring for patients receiving anticoagulation to support continuous renal replacement therapy.

Loneliness and type 2 diabetes incidence: findings from the English Longitudinal Study of Ageing.

AIMS/HYPOTHESIS: Loneliness is associated with all-cause mortality and coronary heart disease. However, the prospective relationship between loneliness and type 2 diabetes onset is unclear. METHODS: We conducted a longitudinal observational population study with data on 4112 diabetes-free participants (mean age 65.02 ± 9.05) from the English Longitudinal Study of Ageing. Loneliness was assessed in 2004-2005 using the revised University of California, Los Angeles (UCLA) Loneliness Scale. Incident type 2 diabetes cases were assessed from 2006 to 2017. Associations were modelled using Cox proportional hazards regression, adjusting for potential confounders, which included cardiometabolic comorbidities. RESULTS: A total of 264 (6.42%) participants developed type 2 diabetes over the follow-up period. Loneliness was a significant predictor of incident type 2 diabetes (HR 1.46; 95% CI 1.15, 1.84; p = 0.002) independent of age, sex, ethnicity, wealth, smoking status, physical activity, alcohol consumption, BMI, HbA1c, hypertension and cardiovascular disease. Further analyses detected an association between loneliness and type 2 diabetes onset (HR 1.41; 95% CI 1.04, 1.90; p = 0.027), independent of depressive symptoms, living alone and social isolation. Living alone and social isolation were not significantly associated with type 2 diabetes onset. CONCLUSIONS/INTERPRETATION: Loneliness is a risk factor for type 2 diabetes. The mechanisms underlying this relationship remain to be elucidated. Graphical abstract.

Predictors of Hypophosphatemia and Outcomes during Continuous Renal Replacement Therapy.

INTRODUCTION: Hypophosphatemia occurs in up to 80% of patients undergoing continuous renal replacement therapy (CRRT) and has been associated with poor outcomes. Whether preemptive phosphate supplementation is warranted in select patients has not been adequately explored. This single-center, retrospective cohort study evaluates predictors of hypophosphatemia and characterizes treatment approaches in adult patients undergoing at least 12 h of CRRT. METHODS: Patients were divided into 2 groups based on the presence or absence of hypophosphatemia as defined by serum phosphorus <2.5 mg/dL. Select laboratory values at baseline and during CRRT, medications and nutritional sources affecting phosphorus, and CRRT parameters were compared. Patient outcomes including resolution of acute kidney injury (AKI), freedom from renal replacement therapy at hospital discharge, duration of intensive care unit (ICU) and hospital stay, duration of mechanical ventilation, and ICU mortality were evaluated. RESULTS: Seventy-two patients were included. The group was 43% female and 51% African American. CRRT was ordered for AKI in 83% and for end-stage renal disease in 15%. Hypophosphatemia occurred in 45 patients (63%). Mean time to development of hypophosphatemia was 34 ± 22 h. Patients who developed hypophosphatemia received a longer duration of CRRT (p = 0.001), were more likely to have a diet ordered (p = 0.005), less likely to have received calcium infusions (p = 0.045), and had lower phosphorus (p = 0.017) and potassium levels (p = 0.038) and higher calcium levels at baseline (p = 0.048). Development of hypophosphatemia was associated with an increased duration of ICU stay (p = 0.014) but not with the other patient outcomes evaluated. Twenty-seven of the 45 patients (60%) who developed hypophosphatemia received phosphorus supplementation with near equal use of intravenous, oral, and combination routes. Only 17 patients (38%) achieved resolution of hypophosphatemia while on CRRT. CONCLUSION: Hypophosphatemia is common, difficult to correct, and contributes to longer ICU stays in patients requiring CRRT. A preemptive approach to address hypophosphatemia including aggressive supplementation strategies to correct phosphorus is warranted in patients requiring CRRT.

Factors Associated With Increased Hospital Length of Stay in Peritoneal Dialysis Patients With Peritonitis: A Need for Antimicrobial Stewardship?

Background: Peritonitis remains a complication of peritoneal dialysis (PD) and contributes to morbidity. Adherence to evidence-based recommendations should resolve peritonitis within 5 days; however, hospital length of stay (LOS) for patients with PD-associated peritonitis (PDAP) varies. Factors contributing to increased LOS and vigilance with antimicrobial stewardship (ASP) in this population are not well described. Methods: This was a system-wide, retrospective cohort of adult patients presenting with PDAP from August 2012 to August 2017. Patients were divided into 2 groups based on LOS: <7 days (reduced LOS) versus ≥7 days (prolonged LOS). Patient demographics, resolution of peritonitis by day 5, intensive care unit (ICU) admission, infectious diseases (ID) consultation, changes in dialysis modality, blood glucose, and pathogen/antimicrobial characteristics were compared. In-hospital mortality and 30-day readmissions were also evaluated. Results: Of the 401 patients screened, 90 were included: 53% women, 88% African American, age 52 ± 2 years (reduced LOS: 46 patients; prolonged LOS: 44 patients). Increased LOS was associated with ICU admission (P = .014), ID consultation (P = .015), PD catheter removal (P = .001), hemodialysis conversion (P < .001), antifungal therapy (P = .021), and days with blood glucose >180 mg/dL (P = .028). Opportunities for antimicrobial de-escalation were identified in 24 (52%) and 22 (50%) patients in the reduced and prolonged LOS groups, respectively; however, de-escalation occurred in only 5 (21%) and 6 (27%) of these patients. There were no differences in mortality or 30-day readmissions. Conclusions: Longer LOS was influenced by acuity of illness and possibly lack of enforced ASP. Improvement of ASP within the PDAP population is necessary.

Adipose tissue loss and lipodystrophy in xylosyltransferase II deficient mice.

BACKGROUND/OBJECTIVES: The cellular and extracellular matrix (ECM) interactions that regulate adipose tissue homeostasis are incompletely understood. Proteoglycans (PGs) and their sulfated glycosaminoglycans (GAGs) provide spatial and temporal signals for ECM organization and interactions with resident cells by impacting growth factor and cytokine activity. Therefore, PGs and their GAGs could be significant to adipose tissue homeostasis. The purpose of this study was to determine the role of ECM sulfated GAGs in adipose tissue homeostasis. METHODS: Adipose tissue and metabolic homeostasis in mice deficient in xylosyltransferase 2 (Xylt2-/-) were examined by histologic analyses, gene expression analyses, whole body fat composition measurements, and glucose tolerance test. Adipose tissue inflammation and adipocyte precursors were characterized by flow cytometry and in vitro culture of mesenchymal stem cells. RESULTS: Xylt2-/- mice have low body weight due to overall reductions in abdominal fat deposition. Histologically, the adipocytes are reduced in size and number in both gonadal and mesenteric fat depots of Xylt2-/- mice. In addition, these mice are glucose intolerant, insulin resistant, and have increased serum triglycerides as compared to Xylt2 + / + control mice. Furthermore, the adipose tissue niche has increased inflammatory cells and enrichment of proinflammatory factors IL6 and IL1ß, and these mice also have a loss of adipose tissue vascular endothelial cells. Lastly, xylosyltransferease-2 (XylT2) deficient mesenchymal stem cells from gonadal adipose tissue and bone marrow exhibit impaired adipogenic differentiation in vitro. CONCLUSIONS: Decreased GAGs due to the loss of the key GAG assembly enzyme XylT2 causes reduced steady state adipose tissue stores leading to a unique lipodystrophic model. Accumulation of an adipocytic precursor pool of cells is discovered indicating an interruption in differentiation. Therefore, adipose tissue GAGs are important in the homeostasis of adipose tissue by mediating control of adipose precursor development, tissue inflammation, and vascular development.

Is successful treatment of depression in dialysis patients an achievable goal?

Depression is undisputedly common among individuals with End-Stage Kidney Failure and associated with adverse outcomes. It is well recognized that effective treatments for depression are needed within routine dialysis care. But, are we any closer to successfully treating depression in dialysis patients? We consider this question here with respect to two common treatments, antidepressant medication and cognitive behavioural therapy (CBT). Currently, there are limited data from randomized placebo-controlled trials regarding the acceptability and efficacy of antidepressants. CBT trials appear to show more consistent treatment effects, albeit the feasibility of routine delivery remains unknown. No studies in dialysis patients has evaluated the combined effects of CBT with antidepressants. There is a need to consider pragmatic depression treatment trials in dialysis patients in order to increase study recruitment in order to have more reliable data from which to evaluate the evidence base. Furthermore, we need to understand why treatments work, and for whom do they work? Lastly, addressing issues surrounding treatment acceptability and implementation as part of regular care remain as key challenges that require attention if we are to improve the mental health of individuals on dialysis.

End-Stage Renal Disease Increases Rates of Adverse Glucose Events When Treating Diabetic Ketoacidosis or Hyperosmolar Hyperglycemic State.

IN BRIEF Treatment guidelines for diabetic emergencies are well described in patients with normal to moderately impaired kidney function. However, management of patients with end-stage renal disease (ESRD) is an ongoing challenge. This article describes a retrospective study comparing the rates of adverse glucose events (defined as hypoglycemia or a decrease in glucose >200 mg/dL/h) between patients with ESRD and those with normal kidney function who were admitted with diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS). These results indicate that current treatment approaches to DKA or HHS in patients with ESRD are suboptimal and require further evaluation.

The Use of Intraperitoneal Ampicillin in a Patient With Enterococcus faecalis Peritonitis.

INTRODUCTION: Peritoneal dialysis (PD) - associated peritonitis is a serious complication of peritoneal dialysis (PD). The 2022 International Society of Peritoneal Dialysis (ISPD) guidelines do not recommend intraperitoneal (IP) ampicillin for treatment of Enterococcal PD - associated peritonitis. To date, there is no in vivo data to support use of IP ampicillin for the treatment of Enterococcus faecalis. CASE DESCRIPTION: A 69-year-old man with a past medical history of end stage kidney disease (ESKD) requiring continuous cycling peritoneal dialysis (CCPD) was admitted to the hospital and treated for peritonitis with E. faecalis. The patient's CCPD prescription was 2.5% Dianeal with 5 total exchanges. IP ampicillin was added to the first 4 exchanges and additional ampicillin was added to the last fill. The patient successfully completed the treatment course with clinical cure. DISCUSSION: The use of IP ampicillin for E. faecalis peritonitis is controversial and previously lacked compelling clinical evidence for or against its use. This case demonstrates treatment of peritonitis using a modified dosing strategy with ampicillin added to each CCPD exchange and last fill. The loss of ampicillin antimicrobial activity reported in vitro with E. faecalis was not supported by this case.

Do interventions for mood improve inflammatory biomarkers in inflammatory bowel disease?: a systematic review and meta-analysis.

BACKGROUND: Psychoneuroimmunological mechanisms and the gut-brain axis appear relevant to disease activity and progression in Inflammatory Bowel Disease (IBD). A recent review showed no effect of psychological therapies on self-reported disease activity in IBD. This meta-analysis aims to establish whether interventions targeting mood outcomes (e.g., depression, anxiety and stress) impact inflammation levels in IBD and possible moderators of these effects. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We searched five electronic databases and included randomised controlled trials where interventions targeted mood and assessed inflammatory outcomes pre- and post-intervention in adults with IBD. Independent reviewers screened studies, extracted data, and assessed methodological quality. Data were pooled to estimate standardised mean differences (SMDs) with 95% Confidence Intervals (CIs). A random-effects robust variance estimation accounted for studies measuring multiple biomarkers. Intervention type, mood as a primary or secondary outcome, effect on mood outcomes and IBD subtype were investigated as treatment effect moderators. Where there were sufficient biomarkers, individual meta-analyses were run (Pre-registration PROSPERO: CRD42023389401). FINDINGS: 28 RCTs involving 1789 participants met inclusion criteria. Interventions demonstrated small, statistically significant effects on biomarkers (-0.35, 95% CI: -0.48, -0.22, p < 0.001) and medium effects on mood outcomes (-0.50, 95% CI: -0.73, -0.27, p < 0.001), without evidence of substantive heterogeneity or publication bias. Individual analyses showed small effects for improved faecal calprotectin (-0.19, 95% CI: -0.34, -0.03, p = 0.018) and C-Reactive Protein (-0.29, 95% CI: -0.47, -0.10, p = 0.002). Effect sizes were larger for psychological therapy interventions (compared with exercise or antidepressants) and when there was an effect (SMD ≥0.2) on mood. INTERPRETATION: Treatments which address mood outcomes have beneficial effects on generic inflammation as well as disease-specific biomarkers (faecal calprotectin and C-Reactive Protein). Psychological interventions and interventions with larger treatment effects on mood accentuated the effect on biomarkers. More research is required to understand the biological or behavioural mechanisms underlying this effect. FUNDING: The Medical Research Council and the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre.

Approaches to the identification and management of depression in people living with chronic kidney disease: A scoping review of 860 papers.

BACKGROUND: Depression is prevalent across the spectrum of Chronic Kidney Disease and associated with poorer outcomes. There is limited evidence regarding the most effective interventions and care pathways for depression in Chronic Kidney Disease. OBJECTIVES: To investigate how depression is identified and managed in adults with Chronic Kidney Disease. DESIGN: Scoping review. METHODS: Systematic search of eight databases with pre-defined inclusion criteria. Data relevant to the identification and/or management of depression in adults with Chronic Kidney Disease were extracted. RESULTS: Of 2147 articles identified, 860 were included. Depression was most identified using self-report screening tools (n = 716 studies, 85.3%), with versions of the Beck Depression Inventory (n = 283, 33.7%) being the most common. A total of 123 studies included data on the management of depression, with nonpharmacological interventions being more frequently studied (n = 55, 45%). Cognitive Behavioural Therapy (n = 15) was the most common nonpharmacological intervention, which was found to have a significant effect on depressive symptoms compared to controls (n = 10). However, how such approaches could be implemented as part of routine care was not clear. There was limited evidence for antidepressants use in people with Chronic Kidney Disease albeit in a limited number of studies. CONCLUSIONS: Depression is commonly identified using validated screening tools albeit differences exist in reporting practices. Evidence regarding the management of depression is mixed and requires better-quality trials of both pharmacological and nonpharmacological approaches. Understanding which clinical care pathways are used and their evidence, may help facilitate the development of kidney care specific guidelines for the identification and management of depression.

The identification and management of depression in UK Kidney Care: Results from the Mood Maps Study.

BACKGROUND: Depression is common in people with chronic kidney disease, yet little is known about how depression is identified and managed as part of routine kidney care. OBJECTIVES: The primary objective was to survey all UK adult kidney centres to understand how depression is identified and managed. A secondary objective was to broadly describe the variability in psychosocial care. DESIGN: Online survey. METHODS: The survey comprised of three sections: (1) general kidney care, (2) psychological provision and (3) social work provision. RESULTS: 48/68 (71%) of centres responded to the general survey with 20 and 13 responses from psychological and social work module respectively. Only 31.4% reported having both in centre psychological and social work practitioners. Three centres reported no access to psychosocial provision. Of the 25 centres who reported on pathways, 36.0% reported having internal pathways for the identification and management of depression. Within services with psychological provision, screening for depression varied across modality/group (e.g., 7.1% in mild/moderate chronic kidney disease vs. 62.5% in kidney donors). Cognitive Behavioural Therapy and Acceptance and Commitment Therapy were the most common interventions offered. Most psychosocial services were aware of the National Institute for Health and Care Excellence guidelines for managing depression in long-term conditions (n = 18, 94.7%) yet few fully utilised (n = 6, 33.3%). Limited workforce capacity was evident. CONCLUSIONS: There is considerable variability in approaches taken to identify and treat depression across UK kidney services, with few services having specific pathways designed to detect and manage depression. Workforce capacity remains a significant issue.

Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants?

BACKGROUND: Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. METHODS: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). DISCUSSION: The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.