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.

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.

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.

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.

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.

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.

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.

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.

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.

Extracellular vesicle small RNA cargo discriminates non-cancer donors from pediatric B-lymphoblastic leukemia patients.

Pediatric B-acute lymphoblastic leukemia (B-ALL) is a disease of abnormally growing B lymphoblasts. Here we hypothesized that extracellular vesicles (EVs), which are nanosized particles released by all cells (including cancer cells), could be used to monitor B-ALL severity and progression by sampling plasma instead of bone marrow. EVs are especially attractive as they are present throughout the circulation regardless of the location of the originating cell. First, we used nanoparticle tracking analysis to compare EVs between non-cancer donor (NCD) and B-ALL blood plasma; we found that B-ALL plasma contains more EVs than NCD plasma. We then isolated EVs from NCD and pediatric B-ALL peripheral blood plasma using a synthetic peptide-based isolation technique (Vn96), which is clinically amenable and isolates a broad spectrum of EVs. RNA-seq analysis of small RNAs contained within the isolated EVs revealed a signature of differentially packaged and exclusively packaged RNAs that distinguish NCD from B-ALL. The plasma EVs contain a heterogenous mixture of miRNAs and fragments of long non-coding RNA (lncRNA) and messenger RNA (mRNA). Transcripts packaged in B-ALL EVs include those involved in negative cell cycle regulation, potentially suggesting that B-ALL cells may use EVs to discard gene sequences that control growth. In contrast, NCD EVs carry sequences representative of multiple organs, including brain, muscle, and epithelial cells. This signature could potentially be used to monitor B-ALL disease burden in pediatric B-ALL patients via blood draws instead of invasive bone marrow aspirates.

Internet-delivered cognitive behavioural therapy programme to reduce depressive symptoms in patients with multiple sclerosis: a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Depression is three to four times more prevalent in patients with neurological and inflammatory disorders than in the general population. For example, in patients with multiple sclerosis, the 12-month prevalence of major depressive disorder is around 25% and it is associated with a lower quality of life, faster disease progression, and higher morbidity and mortality. Despite its clinical relevance, there are few treatment options for depression associated with multiple sclerosis and confirmatory trials are scarce. We aimed to evaluate the safety and efficacy of a multiple sclerosis-specific, internet-based cognitive behavioural therapy (iCBT) programme for the treatment of depressive symptoms associated with the disease. METHODS: This parallel-group, randomised, controlled, phase 3 trial of an iCBT programme to reduce depressive symptoms in patients with multiple sclerosis was carried out at five academic centres with large outpatient care units in Germany and the USA. Patients with a neurologist-confirmed diagnosis of multiple sclerosis and depressive symptoms were randomly assigned (1:1:1; automated assignment, concealed allocation, no stratification, no blocking) to receive treatment as usual plus one of two versions of the iCBT programme Amiria (stand-alone or therapist-guided) or to a control condition, in which participants received treatment as usual and were offered access to the iCBT programme after 6 months. Masking of participants to group assignment between active treatment and control was not possible, although raters were masked to group assignment. The predefined primary endpoint, which was analysed in the intention-to-treat population, was severity of depressive symptoms as measured by the Beck Depression Inventory-II (BDI-II) at week 12 after randomisation. This trial is registered at ClinicalTrials.gov, NCT02740361, and is complete. FINDINGS: Between May 3, 2017, and Nov 4, 2020, we screened 485 patients for eligibility. 279 participants were enrolled, of whom 101 were allocated to receive stand-alone iCBT, 85 to receive guided iCBT, and 93 to the control condition. The dropout rate at week 12 was 18% (50 participants). Both versions of the iCBT programme significantly reduced depressive symptoms compared with the control group (BDI-II between-group mean differences: control vs stand-alone iCBT 6·32 points [95% CI 3·37-9·27], p<0·0001, effect size d=0·97 [95% CI 0·64-1·30]; control vs guided iCBT 5·80 points [2·71-8·88], p<0·0001, effect size d=0·96 [0·62-1·30]). Clinically relevant worsening of depressive symptoms was observed in three participants in the control group, one in the stand-alone iCBT group, and none in the guided iCBT group. No occurrences of suicidality were observed during the trial and there were no deaths. INTERPRETATION: This trial provides evidence for the safety and efficacy of a multiple sclerosis-specific iCBT tool to reduce depressive symptoms in patients with the disease. This remote-access, scalable intervention increases the therapeutic options in this patient group and could help to overcome treatment barriers. FUNDING: National Multiple Sclerosis Society (USA).

An online acceptance, commitment, and self-compassion based treatment to decrease psychological distress in people with type 2 diabetes: A feasibility randomised-controlled trial.

Background and purpose: This study explored the feasibility and acceptability of conducting a larger trial of a self-guided, online self-compassion and acceptance and commitment therapy (ACT) focused treatment among people with type 2 diabetes (T2D) to decrease psychological distress. Materials and methods: This study was a two-arm, parallel, feasibility randomised controlled trial with nested qualitative methods. UK adults with T2D were randomly (1:1) allocated to a five-week online self-compassion and ACT treatment or waitlist control. Information regarding recruitment, trial retention, and treatment completion was collected, and post-treatment semi-structured interviews were conducted to assess feasibility and acceptability. Self-report measures of psychological distress (depression, anxiety, diabetes distress) and potential treatment processes (self-compassion and psychological flexibility) were completed as secondary feasibility outcomes. Results: Fifty-five (60.44 %) out of 91 people who accessed the study link were eligible to participate. Of these, 33 eligible participants (60 %) were randomly assigned to treatment (n = 19) or control arms (waitlist; n = 14). While treatment completion was 47.37 %, trial retention rates were 39.39 % (5-week follow-up) and 21.2 % (9-week follow-up). Secondary feasibility outcomes of treatment effect estimates are difficult to interpret in light of low treatment completion and trial retention rates. Conclusion: A larger trial of the self-guided, online self-compassion treatment to decrease psychological distress in people with T2D may be beneficial, but it has limited feasibility in its current form. Further efforts are needed to improve treatment acceptability of online self-compassion and ACT focused treatment and trial procedures.

A cognitive-behavioural therapy programme for managing depression and anxiety in long-term physical health conditions: mixed-methods real-world evaluation of the COMPASS programme.

BACKGROUND: Mental health comorbidities are common in physical long-term health conditions. AIMS: We evaluate the effectiveness of COMPASS, a therapist-supported, digital cognitive-behavioural therapy programme specifically designed to treat anxiety/depression in the context of long-term conditions. We also investigate patient experiences of the programme. METHOD: We utilised a mixed-methods, non-randomised design. We analysed pre-post data from 76 patients with long-term conditions who were receiving psychological treatment (COMPASS) via local NHS services, using paired sample t-tests and Cohen's d, with depression, anxiety, distress and functional impairment self-report scales. Qualitative interviews explored patients' experiences of using COMPASS. Twenty-one semi-structured interviews were completed and underwent inductive thematic analysis. RESULTS: Patients who received COMPASS had significantly reduced depression (-2.47, 95% CI -3.7 to -1.3, P < 0.001; Cohen's d = -0.376), anxiety (-2.30, 95% CI -3.6 to -1.2, P < 0.001; Cohen's d = -0.420) and psychological distress (-4.87, 95% CI -7.0 to -2.7, P < 0.001; Cohen's d = -0.422) and significantly improved functional impairment (-3.00, 95% CI -4.8 to -1.2, P ≤ 0.001; Cohen's d = -0.282). Effect sizes were larger when analyses included only patients with clinically significant baseline symptoms: depression (-4.02, 95% CI -5.6 to -2.5, P < 0.001; Cohen's d = -0.701), anxiety (-3.60, 95% CI -5.3 to -1.9, P < 0.001; Cohen's d = -0.739), psychological distress (-5.58, 95% CI -7.9 to -3.2, P < 0.001; Cohen's d = -0.523), functional impairment (-3.28, 95% CI -5.4 to -1.1, P ≤ 0.001; Cohen's d = -0.355). Qualitative analysis yielded two meta-themes: engagement and integration of mental and physical health. CONCLUSIONS: Results suggest that COMPASS is effective in NHS settings, and is acceptable to patients. Content tailored to long-term conditions, therapist support and clear delivery strategies should be prioritised to aid intervention implementation.

Gout incidence and management during the COVID-19 pandemic in England, UK: a nationwide observational study using OpenSAFELY.

BACKGROUND: Gout is the most prevalent inflammatory arthritis, yet one of the worst managed. Our objective was to assess how the COVID-19 pandemic impacted incidence and quality of care for people with gout in England, UK. METHODS: With the approval of National Health Service England, we did a population-level cohort study using primary care and hospital electronic health record data for 17·9 million adults registered with general practices using TPP health record software, via the OpenSAFELY platform. The study period was from March 1, 2015, to Feb 28, 2023. Individuals aged 18-110 years were defined as having incident gout if they were assigned index diagnostic codes for gout, were registered with TPP practices in England for at least 12 months before diagnosis, did not receive prescriptions for urate-lowering therapy more than 30 days before diagnosis, and had not been admitted to hospital or attended an emergency department for gout flares more than 30 days before diagnosis. Outcomes assessed were incidence and prevalence of people with recorded gout diagnoses, incidence of gout hospitalisations, initiation of urate-lowering therapy, and attainment of serum urate targets (≤360 µmol/L). FINDINGS: From a reference population of 17 865 145 adults, 246 695 individuals were diagnosed with incident gout. The mean age of individuals with incident gout was 61·3 years (SD 16·2). 66 265 (26·9%) of 246 695 individuals were female, 180 430 (73·1%) were male, and 189 035 (90·9%) of 208 050 individuals with available ethnicity data were White. Incident gout diagnoses decreased by 30·9% in the year beginning March, 2020, compared with the preceding year (1·23 diagnoses vs 1·78 diagnoses per 1000 adults). Gout prevalence was 3·07% in 2015-16, and 3·21% in 2022-23. Gout hospitalisations decreased by 30·1% in the year commencing March, 2020, compared with the preceding year (9·6 admissions vs 13·7 admissions per 100 000 adults). Of 228 095 people with incident gout and available follow-up, 66 560 (29·2%) were prescribed urate-lowering therapy within 6 months. Of 65 305 individuals who initiated urate-lowering therapy with available follow-up, 16 790 (25·7%) attained a serum urate concentration of 360 µmol/L or less within 6 months of urate-lowering therapy initiation. In interrupted time-series analyses, urate-lowering therapy prescribing improved modestly during the pandemic, compared with pre-pandemic, whereas urate target attainment was similar. INTERPRETATION: Using gout as an exemplar disease, we showed the complexity of how health care was impacted during the COVID-19 pandemic. We observed a reduction in gout diagnoses but no effect on treatment metrics. We showed how country-wide, routinely collected data can be used to map disease epidemiology and monitor care quality. FUNDING: None.

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.

Education Standards for Pharmacists Providing Comprehensive Medication Management in Outpatient Nephrology Settings.

Chronic kidney disease is a public health problem that has generated renewed interest due to poor patient outcomes and high cost. The Advancing American Kidney Health initiative aimed to transform kidney care with goals of decreasing the incidence of kidney failure and increasing the number of patients receiving home dialysis or a kidney transplant. New value-based models of kidney care that specify inclusion of pharmacists as part of the kidney care team were developed to help achieve these goals. To support this Advancing American Kidney Health-catalyzed opportunity for pharmacist engagement, the pharmacy workforce must have a fundamental knowledge of the core principles needed to provide comprehensive medication management to address chronic kidney disease and the common comorbid conditions and secondary complications. The Advancing Kidney Health through Optimal Medication Management initiative was created by nephrology pharmacists with the vision that every person with kidney disease receives optimal medication management through team-based care that includes a pharmacist to ensure medications are safe, effective, and convenient. Here, we propose education standards for pharmacists providing care for individuals with kidney disease in the outpatient setting to complement proposed practice standards.

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.

Evaluation of Hospitalized Patients Receiving High versus Low-Dose Opioids for Non-Cancer Pain.

Limited studies suggest that opioid-related adverse effects (ORAEs) may worsen hospitalized patient outcomes, but there is insufficient data related to the impact of high-dose opioids compared to low-dose on adverse patient events. Given the paucity of data, our study aims to evaluate these ORAEs in the general hospitalized patient with non-cancer pain. A retrospective study of adult patients receiving opioids with a primary diagnoses of myocardial infarction, chronic obstructive pulmonary disease, heart failure, pneumonia, sepsis, or diabetes was conducted. Average oral morphine milligram equivalents (MMEs) administered over the entire LOS was collected, and patients were categorized as high-dose (≥50 MMEs/day) or low-dose (<50 MMEs/day). The primary composite endpoint was the incidence of ORAEs (naloxone use, decreased oxygen saturations, nausea/vomiting). Secondary outcomes included LOS, 30-day readmission, ORAEs with >100 MMEs/day. A total of 100 patients were included (n = 58 low-dose group; n = 42 high-dose group). For the primary outcome, more patients in the high-dose group experienced ORAEs (50% high-dose vs. 22.4% low-dose; p < 0.006). No statistically significant differences in LOS or 30-day readmission rates were identified between the groups. For patients receiving >100 MMEs/day, ORAEs occurred in 61% of patients. Hospitalized patients receiving high-dose opioids for non-cancer pain may have an increased incidence of ORAEs.

Mental health outcomes in patients with a long-term condition: analysis of an Improving Access to Psychological Therapies service.

BACKGROUND: Having a long-term condition (LTC) significantly affects mental health. UK policy requires effective mental health provisions for patients with an LTC, generally provided by Improving Access to Psychological Therapies (IAPT) services. National IAPT data suggest that patients with an LTC typically demonstrate poorer outcomes compared with patients without an LTC. However, exploration of confounding factors and different outcome variables is limited. AIMS: To establish the association of LTC status with demographic and clinical factors, and clinical mental health outcomes. METHOD: Anonymised patient-level data from a London IAPT service during January 2019 to October 2020 were used in this cohort study, to compare differences between LTC and non-LTC groups on sociodemographic and clinical variables. Binary logistic and multiple linear regression models were constructed for binary outcome variables (recovery and reliable improvement) and continuous outcomes (distress and functioning), respectively. RESULTS: Patients with an LTC were more likely to be female; older; from a Black, mixed or other ethnic background; and have greater social deprivation. Across the four clinical outcomes (recovery, reliable improvement, final psychological distress and final functioning), having an LTC significantly predicted poorer outcomes even after controlling for sociodemographic and clinical baseline variables. For three outcome variables, greater social deprivation and being discharged during the COVID-19 pandemic also predicted poorer clinical outcomes. CONCLUSIONS: LTC status has a negative effect on mental health outcomes in IAPT services, independent of associated variables such as severity of baseline mental health symptoms, ethnicity and social deprivation. Effective psychological treatment for patients with an LTC remains an unresolved priority.