Estimation of the burden of shielding among a cross-section of patients attending rheumatology clinics with SLE-data from the BSR audit of systemic lupus erythematosus.

OBJECTIVES: We aimed to estimate what proportion of people with SLE attending UK rheumatology clinics would be categorized as being at high risk from coronavirus disease 2019 (COVID-19) and therefore asked to shield, and explore what implications this has for rheumatology clinical practice. METHODS: We used data from the British Society for Rheumatology multicentre audit of SLE, which included a large, representative cross-sectional sample of patients attending UK Rheumatology clinics with SLE. We calculated who would receive shielding advice using the British Society for Rheumatology's risk stratification guidance and accompanying scoring grid, and assessed whether ethnicity and history of nephritis were over-represented in the shielding group. RESULTS: The audit included 1003 patients from 51 centres across all 4 nations of the UK. Overall 344 (34.3%) patients had a shielding score ≥3 and would have been advised to shield. People with previous or current LN were 2.6 (1.9-3.4) times more likely to be in the shielding group than people with no previous LN (P < 0.001). Ethnicity was not evenly distributed between the groups (chi-squared P < 0.001). Compared with White people, people of Black ethnicity were 1.9 (1.3-2.8) and Asian 1.9 (1.3-2.7) times more likely to be in the shielding group. Increased risk persisted after controlling for LN. CONCLUSION: Our study demonstrates the large number of people with SLE who are likely to be shielding. Implications for clinical practice include considering communication across language and cultural differences, and ways to conduct renal assessment including urinalysis, during telephone and video consultations for patients who are shielding.

BSR guideline on the management of adults with systemic lupus erythematosus (SLE) 2018: baseline multi-centre audit in the UK.

OBJECTIVES: To assess the baseline care provided to patients with SLE attending UK Rheumatology units, audited against standards derived from the recently published BSR guideline for the management of adults with SLE, the NICE technology appraisal for belimumab, and NHS England's clinical commissioning policy for rituximab. METHODS: SLE cases attending outpatient clinics during any 4-week period between February and June 2018 were retrospectively audited to assess care at the preceding visit. The effect of clinical environment (general vs dedicated CTD/vasculitis clinic and specialized vs non-specialized centre) were tested. Bonferroni's correction was applied to the significance level. RESULTS: Fifty-one units participated. We audited 1021 episodes of care in 1003 patients (median age 48 years, 74% diagnosed >5 years ago). Despite this disease duration, 286 (28.5%) patients had active disease. Overall in 497 (49%) clinic visits, it was recorded that the patient was receiving prednisolone, including in 28.5% of visits where disease was assessed as inactive. Low documented compliance (<60% clinic visits) was identified for audit standards relating to formal disease-activity assessment, reduction of drug-related toxicity and protection against comorbidities and damage. Compared with general clinics, dedicated clinics had higher compliance with standards for appropriate urine protein quantification (85.1% vs 78.1%, P ≤ 0.001). Specialized centres had higher compliance with BILAG Biologics Register recruitment (89.4% vs 44.4%, P ≤ 0.001) and blood pressure recording (95.3% vs 84.1%). CONCLUSIONS: This audit highlights significant unmet need for better disease control and reduction in corticosteroid toxicity and is an opportunity to improve compliance with national guidelines. Higher performance with nephritis screening in dedicated clinics supports wider adoption of this service-delivery model.

Propofol-induced Inhibition of Catecholamine Release Is Reversed by Maintaining Calcium Influx.

BACKGROUND: Propofol (2,6-diisopropylphenol) is one of the most frequently used anesthetic agents. One of the main side effects of propofol is to reduce blood pressure, which is thought to occur by inhibiting the release of catecholamines from sympathetic neurons. Here, the authors hypothesized that propofol-induced hypotension is not simply the result of suppression of the release mechanisms for catecholamines. METHODS: The authors simultaneously compared the effects of propofol on the release of norepinephrine triggered by high K-induced depolarization, as well as ionomycin, by using neuroendocrine PC12 cells and synaptosomes. Ionomycin, a Ca ionophore, directly induces Ca influx, thus bypassing the effect of ion channel modulation by propofol. RESULTS: Propofol decreased depolarization (high K)-triggered norepinephrine release, whereas it increased ionomycin-triggered release from both PC12 cells and synaptosomes. The propofol (30 µM)-induced increase in norepinephrine release triggered by ionomycin was dependent on both the presence and the concentration of extracellular Ca (0.3 to 10 mM; n = 6). The enhancement of norepinephrine release by propofol was observed in all tested concentrations of ionomycin (0.1 to 5 µM; n = 6). CONCLUSIONS: Propofol at clinically relevant concentrations promotes the catecholamine release as long as Ca influx is supported. This unexpected finding will allow for a better understanding in preventing propofol-induced hypotension.

Relationships of behavioral measures of frontal lobe dysfunction with underlying electrophysiology in cocaine-dependent patients.

BACKGROUND AND OBJECTIVES: Despite evidence that frontal lobe functioning is impaired in cocaine-dependent individuals, relationships between behavioral measures of frontal dysfunction and electrophysiological measures of inhibition in cocaine use have not been explored. METHODS: Using the Frontal Systems Behavior Scale (FrSBe), frontal dysfunction was assessed in a group of abstinent cocaine-dependent subjects (N = 49) and healthy controls (N = 32). Using transcranial magnetic stimulation (TMS) and evoked potential (EP)-based electrophysiological measures of inhibition, we assessed associations between these measures and FrSBe estimates of frontal dysfunction. RESULTS: Patients had significantly higher FrSBe scores for executive dysfunction, disinhibition, and apathy than controls. Lower TMS-based resting motor thresholds (ie, hyperexcitability) were significantly associated with higher executive dysfunction scores in the patients. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Relationships between FrSBe scores and TMS-based measures highlight neurophysiological aberrations underlying frontal lobe dysfunction in cocaine abusers. TMS and EP measures may be useful probes of the intermediary steps between frontal lobe dysfunction and addictive behavior.

To what extent is NICE guidance on the management of rheumatoid arthritis in adults being implemented in clinical practice? A regional survey.

Rheumatoid arthritis (RA) is a chronic disease associated with significant morbidity. The 2009 NICE guidance advises on the management of patients with RA. In this study, we undertook a survey to assess the implementation of the guidance into practice across the Midlands. In total, 19 rheumatology units participated, of which nine have designated early inflammatory arthritis clinics (EIAC). Data for 311 patients with RA attending clinics were collected during a two week period. The median time from symptom onset to first visit was four months. Of the patients, 95.6% were seen within 12 weeks of referral. Of those seen in EIAC, 75.9% had erosions documented on X-rays versus 49.4% of non-EIAC patients. In addition, 57.9% of patients were offered combination disease-modifying antirheumatic drugs (DMARD) therapy in EIAC, versus 30.4% in non-EIAC units. Monthly disease-activity scores were calculated more in patients attending EIAC than non-EIAC units (51.1% versus 25.4%). Based on our results, there is significant regional variation in implementation of the NICE guidance. In addition, patients with RA attending EIACs are more likely to receive a treat-to-target approach.

Efficiency and risk factors for CMV transmission in seronegative hematopoietic stem cell recipients.

Cytomegalovirus (CMV) transmission via stem cells or marrow in CMV donor seropositive/recipient seronegative (D+/R-) hematopoietic cell transplantation (HCT) is surprisingly inefficient, and factors associated with transmission in these high-risk HCT recipients are unknown. In a retrospective cohort of D+/R- HCT recipients, cumulative incidence curve estimates were used to determine posttransplantation rates of CMV and multivariable Cox proportional models to assess risk factors associated with transmission. A total of 447 patients from 1995 to 2007 were eligible for enrollment. Overall, 85 of 447 (19.0%) acquired CMV at a median of 49 days (IQR 41-60) posttransplantation. CMV disease before day 100 occurred in 6 of 447 (1.3%) patients and in 7 of 447 (1.6%) after day 100. The donor graft, specifically the total nucleated cell count (adjusted hazard ratio [HR] 2.7; 95% confidence interval [CI], 1.4-4.7, P = .0002), was the only factor associated with CMV transmission in multivariable analyses. Notably, the source stem cells (marrow versus peripheral blood stem cell [PBSC]), screening method, and graft-versus-host disease (GVHD) were not associated with transmission. Thus, a highly cellular graft was the only identifiable risk factor associated with CMV transmission, suggesting that viral genomic content of the donor graft determines transmission efficiency in D+/R- HCT recipients.

Compliance with NICE guidance on the use of anti-TNFalpha agents in ankylosing spondylitis: an east and west Midlands regional audit.

Here we report on an audit performed to examine compliance with National Institute for Health and Clinical Excellence (NICE) guidelines for the use of anti-tumour necrosis factor alpha (anti-TNFalpha) in treating patients with ankylosing spondylitis (AS). Data from 17 rheumatology centres across the Midlands were collected prospectively from patients with AS attending outpatient clinics and retrospectively in patients receiving anti-TNFalpha but not attending outpatient clinics during the audit. In total, 80% of the 416 patients for whom data were collected were male. Of the 238 patients recruited prospectively, 41% were receiving anti-TNFalpha. Reviewing all patients on anti-TNFalpha (N=275), pre-treatment assessments 12 weeks apart were documented in 55% of patients. After anti-TNFalpha treatment had started, regular 12-weekly assessments occurred in 46% of patients. Therefore, compliance with NICE guidance was found to vary among centres. Based on our audit, clinical capacity, and clinical or patient choice might be influencing the suboptimal adherence seen in assessment timing suggested by NICE guidelines relating to the use of anti-TNFalpha in treating patients with AS.

Attitudes and perceptions of rheumatologists regarding consultation skills training for specialist trainees: a qualitative study.

Within rheumatology specialty training, direct observation and formal assessment of consultation skills rarely occur. This study explored the attitudes and perceptions of rheumatology specialist registrars (SpRs) and consultants regarding consultation skills training and potential barriers to its successful implementation in the context of specialist training. Semi-structured interviews with rheumatology consultants and focus groups with rheumatology SpRs were conducted in four UK deanery regions. All participants value consultation skills training and believe it requires observation of trainees consulting. The skills of consultant trainers in providing feedback on consulting skills are sometimes sub-optimal. Direct, real time observation of trainees is difficult and happens infrequently. Recording consultations is a potentially attractive alternative. Important issues regarding the successful implementation of videotaped consultations include time constraints, consistency in the assessment of consultation skills, and expertise in providing constructive feedback that is individualised and tailored to the trainee's learning needs.

Methodological approaches to the design and analysis of nonrandomized intervention studies for the prevention of child and adolescent obesity.

OBJECTIVES: Interventions for child obesity prevention are needed and it is unclear whether evidence from nonrandomized intervention studies is adequate. The objective of this research was to review the methods for the design, analysis and reporting of nonrandomized intervention studies for child obesity prevention and to assess potential for bias. METHODS: We conducted a review of nonrandomized intervention studies, including population health interventions, quasi-experimental studies and natural experiments, published from 2013 to 2017 that were identified in a recent systematic review. Data on study design, intervention and control groups, outcome measures, and statistical analyses, were extracted. Risk of bias was evaluated using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. RESULTS: All identified studies (n = 23) included a school or community-based intervention and had a concurrent control group. Participants were 3-18 years and sample sizes were 100 to > 1 million. Study designs were described inconsistently, and interventions ranged from 14 weeks to 5 years. Obesity was compared between control and intervention groups using logistic or linear regression, analysis of variance and mixed effects regression. Only 48% of studies accounted for clustering, and methods to control for confounding and repeated measures varied substantially. Overall risk of bias was moderate to serious for all studies. CONCLUSION: There are substantial opportunities to improve the methods for nonrandomized intervention studies and reduce bias. Future studies should use advanced statistical and causal epidemiology methods, including better control for confounding and clustering, to generate higher quality evidence and certainty regarding which obesity prevention interventions are effective.

Latent class analysis of obesity-related characteristics and associations with body mass index among young children.

OBJECTIVE: Identifying how obesity-related characteristics cluster in populations is important to understand disease risk. Objectives of this study were to identify classes of children based on obesity-related variables and to evaluate the associations between the identified classes and overweight and obesity. METHODS: A cross-sectional study was conducted among children 3-11 years of age (n = 5185) from the TARGet Kids! network (2008-2018). Latent class analysis was used to identify distinct classes of children based on 15 family, metabolic, health behaviours and school-related variables. Associations between the identified latent classes and overweight and obesity were estimated using multinomial logistic regression. RESULTS: Six classes were identified: Class 1: 'Family and health risk behaviours' (20%), Class 2: 'Metabolic risk' (7%), Class 3: 'High risk' (6%), Class 4: 'High triglycerides' (21%), Class 5: 'Health risk behaviours and developmental concern' (22%), and Class 6: 'Healthy' (24%). Children in Classes 1-5 had increased odds of both overweight and obesity compared with 'Healthy' class. Class 3 'High risk' was most strongly associated with child overweight (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.2, 3.2) and obesity (OR 3.3, 95% CI 1.7, 6.7). CONCLUSIONS: Distinct classes of children identified based on obesity-related characteristics were all associated with increased obesity; however, the magnitude of risk varied depending on number of at-risk characteristics. Understanding the clustering of obesity characteristics in children may inform precision public health and population prevention interventions.

Associations between non-anaemic iron deficiency and outcomes following surgery for colorectal cancer: An exploratory study of outcomes relevant to prospective observational studies.

Iron deficiency is common in colorectal cancer. Despite perioperative guidelines advocating for the correction of non-anaemic iron deficiency prior to major surgery, the impact of this pathology on postoperative outcome is unclear. We conducted a single-centre, historical cohort study of 141 elective resections for colorectal cancer. We stratified non-anaemic patients into iron deficient and iron replete groups, and collected data on baseline characteristics, preoperative laboratory results, intraoperative events and postoperative outcomes. As this study was an exploratory work for future research, a P-value of 0.25 was considered relevant. Patients in the deficient group demonstrated lower baseline ferritin (median (interquartile range, IQR) 76 (41-141) µg/L versus 207 (140-334) µg/L, P < 0.001) and transferrin saturation (mean (standard deviation, SD) 18% (8%) versus 32% (12%), P < 0.001) than those in the replete group, and lower starting haemoglobin (mean (SD) 138 (10) g/L versus 144 (12) g/L, P = 0.01). The deficient group had increased re-admission (25% (24%) versus 4% (11%), P = 0.15) and all-cause infection (25% (24%) versus 5% (14%), P = 0.24). A decrease of two days in days alive and out of hospital at postoperative day 90 was seen in the deficient group on univariate analysis (median (IQR) 81 (75-84) versus 83 (78-84), P = 0.25). This reduced to 1.24 days in multivariate adjusted quantile regression analysis ( P = 0.22). Days alive and out of hospital at day 90, postoperative re-admission and postoperative infection may be meaningful outcome measures for future prospective observational work examining non-anaemic iron deficiency in patients undergoing major surgery for colorectal cancer.

Outcomes and compliance with standards of care in anti-neutrophil cytoplasmic antibody-associated vasculitis-insights from a large multiregion audit.

OBJECTIVES: We aimed to conduct a large audit of routine care for patients with ANCA-associated vasculitis. METHODS: We invited all 34 hospitals within one health region in England to undertake a retrospective case note audit of all patients newly diagnosed or treated with CYC or rituximab (RTX) for ANCA-associated vasculitis from April 2013 to December 2014. We compared clinical practice to the British Society for Rheumatology guidelines for the management of adults with ANCA-associated vasculitis and the use of RTX with the National Health Service (NHS) England commissioning policy and National Institute for Health and Care Excellence (NICE) technology appraisal. RESULTS: We received data from 213 patients. Among 130 newly diagnosed patients, delay from admission to diagnosis ranged from 0 to 53 days (median 6, interquartile range 3-10.5) for those diagnosed as inpatients. BVAS was recorded in 8% of patients at diagnosis. Remission at 6 months was achieved in 83% of patients. The 1-year survival was 91.5%. A total of 130 patients received CYC for new diagnosis or relapse. The correct dose of i.v. CYC (within 100 mg of the target dose calculated for age, weight and creatinine) was administered in 58% of patients. A total of 25% of patients had an infection requiring hospital admission during or within 6 months of completing their CYC therapy. Seventy-six patients received RTX for new diagnosis or relapse. A total of 97% of patients met the NHS England or NICE eligibility criteria. Pneumocystis jiroveci pneumonia prophylaxis (recommended in the summary of product characteristics) was given in only 65% of patients. CONCLUSION: We identified opportunities to improve care, including compliance with safety standards for delivery of CYC. Development of a national treatment protocol/checklist to reduce this heterogeneity in care should be considered as a priority.

Evaluation of early discharge after hospital treatment of neutropenic fever in acute myeloid leukemia (AML).

BACKGROUND: Hospital admission for neutropenic fever in patients with AML is a standard practice. However, discharge practices vary once patients become afebrile, with many patients hospitalized until rise in the absolute neutrophil count (ANC) to >500 (ANC recovery). Data to support this practice are sparse. We hypothesized that patients admitted for neutropenic fever, particularly if in complete remission (CR) or about to enter CR following the chemotherapy course associated with neutropenic fever, might be safely discharged earlier (ED). Benefits of ED are less exposure to hospital pathogens, reduced cost, increased availability of beds for patients more in need of urgent care, and potentially, enhanced psychological well-being. METHODS: We identified patients age 18-70 with newly diagnosed AML who were admitted to the University of Washington Medical Center with neutropenic fever between January 2008 and May 2010. We compared subsequent (within 30 days of discharge) deaths, intensive care unit (ICU) admissions, and readmissions for neutropenic fever according to discharge ANC, regarded as a numerical variable using the Mann-Whitney U test and as <500 vs >500 using the Fisher Exact test. We used the Mann-Whitney U or Spearman correlation to analyze the relation between ANC at discharge and other covariates that might have affected outcome: age, ECOG performance status at admission for neutropenic fever, days inpatient, remission status, and type of infection (pneumonia, gram negative bacteremia, others). RESULTS: We evaluated 49 patients discharged after admission for neutropenic fever, 26 of whom were discharged with an ANC <500. Thirty five of the patients were in CR or entered CR following the chemotherapy course associated with their neutropenic fever admission. Patients who were discharged with lower ANC were more likely to be readmitted with neutropenic fever (Mann-Whitney U p=0.03), although this was not true using ANC categorized as < vs >500 (Fisher Exact p=0.24, 95% confidence interval -0.47, 0.11). There was no relation between ANC at discharge and subsequent admission to an ICU (Mann-Whitney U p=0.50, Fisher Exact p=0.64, 95% confidence interval 0.2, 0.34 using the 500 ANC cut off). One patient died: a 55 year old discharged with ANC 0 after successful treatment of neutropenic fever died 19 days after hospital readmission with fever of unknown origin. Stenotrophomonas maltophilia pneumonia and sepsis were discovered 14 days after readmission. Assuming a beta distribution and rates of death of 1/26 for discharge with ANC<500 and 0/23 for discharge with ANC>500, the probability that a discharge ANC with <500 is associated with a higher death rate is 0.019. The number of events was too small for a multivariate analysis. However, patients with better performance status (