Monitoring indirect impact of COVID-19 pandemic on services for cardiovascular diseases in the UK.

OBJECTIVE: To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects. METHODS: Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019. We analysed aggregate data for selected cardiovascular diseases before and during the epidemic. We produced an online visualisation tool to enable near real-time monitoring of trends. RESULTS: Across nine hospitals, total admissions and emergency department (ED) attendances decreased after lockdown (23 March 2020) by 57.9% (57.1%-58.6%) and 52.9% (52.2%-53.5%), respectively, compared with the previous year. Activity for cardiac, cerebrovascular and other vascular conditions started to decline 1-2 weeks before lockdown and fell by 31%-88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures. Compared with before the first UK COVID-19 (31 January 2020), activity declined across diseases and specialties between the first case and lockdown (total ED attendances relative reduction (RR) 0.94, 0.93-0.95; total hospital admissions RR 0.96, 0.95-0.97) and after lockdown (attendances RR 0.63, 0.62-0.64; admissions RR 0.59, 0.57-0.60). There was limited recovery towards usual levels of some activities from mid-April 2020. CONCLUSIONS: Substantial reductions in total and cardiovascular activities are likely to contribute to a major burden of indirect effects of the pandemic, suggesting they should be monitored and mitigated urgently.

Trust compliance with best practice tariff criteria for total hip and knee replacement.

BACKGROUND: Satisfaction of the best practice tariff criteria for primary hip and knee replacement enables on average an additional £560 of reimbursement per case. The Getting it Right First Time report highlighted poor awareness of these criteria among orthopaedic departments. METHODS: The authors investigated the reasons for non-compliance with the best practice tariff criteria at their trust and implemented a quality improvement approach to ensure successful adherence to the standards (a minimum National Joint Registry compliance rate of 85%, a National Joint Registry unknown consent rate below 15%, a patient-reported outcome measure participation rate of ≥50%, and an average health gain not significantly below the national average). This was investigated using quarterly online reports from the National Joint Registry and NHS Digital. RESULTS: Initially, the trust had a 31% patient-reported outcome measures participation rate arising from a systematic error in the submission of preoperative patient-reported outcome measure scores. Re-audit following the resubmission of patient-reported outcome measure data under the trust's correct organization data service code confirmed an improvement in patient-reported outcome measure compliance to 90% and satisfaction of all criteria resulting in over £450 000 of additional reimbursement to the trust. CONCLUSIONS: The authors would urge others to review their compliance with these four best practice tariff criteria to ensure that they too are not missing out on this significant reimbursement sum.

Assessment of the T-SPOT.CMV interferon-γ release assay in renal transplant recipients: A single center cohort study.

BACKGROUND: The measurement of CMV specific cellular immunity in organ transplant recipients could contribute additional acuity to serology based, CMV infection risk stratification, facilitating optimisation of immunosuppression and anti-viral prophylaxis. METHODS: A pilot study of renal transplant recipient (RTR's) responses in the T-SPOT.CMV ELISPOT based assay. 108 RTR's were recruited 3 months post-transplantation, immediately prior to the cessation of stratified anti-viral prophylaxis, used in recipients from seropositive donors. RTR's were monitored for CMV viremia and disease. Cellular responses to peptides derived from CMV IE1 and pp65 were measured, using the T-SPOT.CMV assay. RESULTS: At recruitment, no CMV specific cellular immunity was detected by T-SPOT.CMV in CMV seronegative recipients (IE1 ≤ 1spot / 2.5x105 PBMC's; pp65 ≤ 3 spots / 2.5x105 PBMC's). At recruitment, CMV sero-positive recipients who made a robust response to both IE1 (>25 spots / 2.5x105 PBMC's) and pp65 (>50 spots / 2.5x105 PBMC's), were less likely to develop high level viremia than those who responded to one or neither antigen (0/28 vs 5/25; p<0.02). CONCLUSIONS: In CMV seronegative RTR's, CMV specific cellular immunity measured by T-SPOT.CMV was not detected prior to cessation of anti-viral prophylaxis. This differs from recent reports of CMV specific cellular immunity in a proportion of CMV seronegative RTR's, associated with protection from CMV infection. In seropositive RTR's, a dual response to IE1 and pp65 at recruitment, was associated with protection from subsequent viremia. This suggests that assessing the diversity of response to CMV antigens, may enhance risk stratification in this group.

Outcomes of anterolateral thigh free flap thinning using liposuction following lower limb trauma.

BACKGROUND: Whilst soft tissue closure is the priority to prevent infection in open fractures of the lower limb, some patients find that bulky flaps interfere with function and dislike the appearance. We report the outcomes of delayed free anterolateral thigh flap thinning with liposuction. MATERIAL AND METHODS: 38 patients treated between 2006 and 2009 were offered flap contouring. 23 chose flap thinning and 15 did not. We measured outcomes using the SF-36v2 questionnaire and cosmetic outcome scores pre and postoperatively at a mean follow up of 12 weeks (range 10-16 weeks). RESULTS: SF-36v2 physical health (PH) scores improved from a mean of 67 preoperatively to 80 postoperatively (p = 0.01) in the thinned group, while mental health (MH) scores remained unchanged (74-72). The mean SF-36v2 scores for the non-thinned group were 77 (PH) and 86 (MH). Following liposuction the median cosmetic outcome scores out of 5 improved from 1 (not at all satisfied) to 4 (very satisfied) postoperatively (p = 0.0005), which was also higher than the non-thinned group (3) [moderately satisfied], p = 0.004). There was no difference in sex, age, BMI and region on the leg of free flap reconstruction between the non-thinned and thinned groups. CONCLUSIONS: Delayed contouring of free ALT flaps used for lower limb reconstruction results in improvements in physical health measures and cosmetic outcomes. Patients not requesting thinning are generally satisfied with their reconstruction.

Mortality prediction after kidney transplantation: comparative clinical use of 7 comorbidity indices.

OBJECTIVES: Despite comorbidity associated with chronic kidney disease, little data exist applying comorbidity scoring systems to renal transplant recipients. This study compared the performance of 7 established comorbidity scores in predicting mortality after kidney transplantation. MATERIALS AND METHODS: We retrospectively analyzed prospectively collected data from 2033 incident renal transplant recipients. Comorbidity was assessed at baseline, and the following scores were derived: Recipient Risk Score, Charlson Comorbidity Index, Age-adjusted Charlson Comorbidity Index, Modified End-Stage Renal Disease Charlson Comorbidity Index, Foley Score, Wright-Khan Index, and Davies Index. Cox models investigated the association of each comorbidity score with mortality; performance characteristics were tested using receiver operating characteristic curve analysis. RESULTS: Age-stratified Cox analyses showed the Recipient Risk Score-based model displayed the best fit, and receiver operating characteristic curve analysis showed the Recipient Risk Score demonstrated greatest predictive use (5-year mortality c-statistic: 0.787). The independent effect of age on mortality was demonstrated after analysis of scores not containing age as a component (the Charlson Comorbidity Index, the Modified End-Stage Renal Disease Charlson Comorbidity Index, the Davies Index); addition of age to these scores improved fit. CONCLUSIONS: Of the currently available comorbidity scores, the Recipient Risk Score demonstrated greatest use. This has implications for deceased-donor allocation algorithms, assessment of confounders in clinical research, and potentially, individual patient management.

The impact of an Acute Knee Clinic.

INTRODUCTION: The aim of this audit was to analyse the impact of an open access clinic for the treatment of soft tissue knee injuries with regard to delay to treatment. PATIENTS AND METHODS: Data from 100 consecutive patients seen in our sports clinic in 2000 were collected. Following this audit, an Acute Knee Clinic was introduced and took place once per week. In 2006, the audit loop was closed and data from 100 consecutive patients seen in the Acute Knee Clinic were collected. RESULTS: The time from injury to the first review by a specialist is referred to as the time to diagnosis. The introduction of the Acute Knee Clinic led to an 89% reduction in the time to diagnosis for accident and emergency referrals and a 32% reduction for general practitioner referrals. The average number of visits of any sort made by the patient prior to review by a specialist in 2000 was five as opposed to one in 2006. CONCLUSIONS: An Acute Knee Clinic with open access is a simple method of dramatically reducing the delay to diagnosis. This decreases the total delay to treatment which is of particular importance in patients requiring anterior cruciate ligament (ACL) reconstruction due to the risk of secondary meniscal and chondral injuries. Decreasing the delay to diagnosis and appropriate treatment reduces the recovery time. This not only reduces the socio-economic cost of soft tissue knee injuries but may also decrease the psychosocial consequences for the patient. By reducing the number of times a patient is seen by medical practitioners prior to review by a specialist has the potential to decrease the total cost of treatment. The socio-economic impact and potential actual cost savings of treatment are particularly important with the current economic climate.

Reaction phenotyping in drug discovery: moving forward with confidence?

For the pharmaceutical industry, one of the challenges in evaluating the risk of future compound attrition at the discovery stage is the successful prediction of the major routes of clearance in humans. For compounds cleared by metabolism, such information will help to avoid the development of compounds that will exhibit large interpatient differences in pharmacokinetics via 1). routes of metabolism catalyzed by functionally polymorphic enzymes and/or 2). clinically significant metabolic drug-drug interactions, in the later stages of development. The degree of intersubject variability that is acceptable for a drug candidate is uncertain in the discovery stage where knowledge of other important factors is limited or unavailable (i.e. therapeutic index, pharmacodynamic variability, etc). Reaction phenotyping is the semi-quantitative in vitro estimation of the relative contributions of specific drug-metabolizing enzymes to the metabolism of a test compound. However, reaction phenotyping in the discovery stage of drug development is complicated by the absence of radiolabelled parent compound or metabolite bioanalytical standards relative to later stages of development. In this commentary, some of the approaches, based on published data, which can be taken to overcome these challenges are discussed. In addition, knowledge of the molecular structure (i.e. specific chemical substituents), physicochemical properties, and routes of clearance in animals can all help in making a successful prediction for the routes of clearance in humans. In combination, the objective of these studies should be to reduce to a minimum the risk of finding significant inter-patient differences in pharmacokinetics at a later stage in development due to significant metabolism by polymorphic enzymes or drug-drug interactions. Consequently, this data should be used to avoid costly late stage attrition.