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Variation in the observed effect of Xpert MTB/RIF testing for tuberculosis on mortality: A systematic review and analysis of trial design considerations.
No full textMost studies evaluating the effect of Xpert MTB/RIF testing for tuberculosis (TB) concluded that it did not reduce overall mortality compared to usual care. We conducted a systematic review to assess whether key study design and execution features contributed to earlier identification of patients with TB and decreased pre-treatment loss to follow-up, thereby reducing the potential impact of Xpert MTB/RIF testing. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Scopus for literature published from 1 January 2009 to February 2019. We included all primary intervention studies that had evaluated the effect of Xpert MTB/RIF on mortality compared to usual care in participants with presumptive pulmonary TB. We critically reviewed features of included studies across: Study setting and context, Study population, Participant recruitment and enrolment, Study procedures, and Study follow-up. We included seven randomised and one non-randomised study. All included studies demonstrated relative reductions in overall mortality in the Xpert MTB/RIF arm ranging from 6% to 40%. However, mortality reduction was reported to be statistically significant in two studies. Study features that could explain the lack of observed effect on mortality included: the higher quality of care at study sites; inclusion of patients with a higher pre-test probability of TB leading to higher than expected empirical rates; performance of additional diagnostic testing not done in usual care leading to increased TB diagnosis or empiric treatment initiation; the recruitment of participants likely to return for follow-up; and involvement of study staff in ensuring adherence with care and follow-up. Most studies of Xpert MTB/RIF were designed and conducted in a manner that resulted in more patients being diagnosed and treated for TB, minimising the potential difference in mortality Xpert MTB/RIF testing could have achieved compared to usual care
Management of new onset loss of sense of smell during the COVID-19 pandemic - BRS Consensus Guidelines.
No full textOBJECTIVES
The primary aim of the study is to provide recommendations for the investigation and management of patients with new onset loss of sense of smellduring the COVID-19 pandemic DESIGN: After undertaking a literature review, we used the RAND/UCLA methodology with a multi-step process to reach consensus about treatment options, onward referral andimaging.
SETTING AND PARTICIPANTS
An expert panel consisting of 15 members was assembled. A literature review was undertaken prior to the study and evidence was summarised for the panellists.
MAIN OUTCOME MEASURES
The panel undertook a process of ranking and classifying appropriateness of different investigations and treatment options for new onset loss of sense of smell during the COVID-19 pandemic.Using a 9-point Likert scale, panellists scored whether a treatment was: Not recommended, optional, or recommended. Consensus was achieved when more than 70% of responses fell into the category defined by the mean.
RESULTS
Consensus was reached on the majority of statements after 2 rounds of ranking. Disagreement meant no recommendation was made regarding one treatment, using Vitamin A Drops. Alpha lipoic acid was not recommended, olfactory training was recommended for all patients with persistent loss of sense of smell of more than 2 weeks duration, and oral steroids, steroid rinses and omega 3 supplements may be considered on an individual basis. Recommendations regarding the need for referral and investigation have been made.
CONCLUSION
This study identified the appropriateness of olfactory training, different medical treatment options, referral guidelines and imaging for patients with COVID-19 related loss of sense of smell. The guideline may evolve as our experience of COVID-19 develops
Publisher Correction: The National Lung Matrix Trial of personalized therapy in lung cancer.
No full textAn amendment to this paper has been published and can be accessed via a link at the top of the paper
Letter: online search trends suggest patient concerns around immunosuppression use in inflammatory bowel disease during COVID-19 in the United Kingdom.
No full textThe effect of the COVID-19 pandemic on skin cancer surgery in the United Kingdom: a national, multi-centre, prospective cohort study and survey of Plastic Surgeons.
No full textAn economic evaluation of the randomised controlled trial of topical corticosteroid and home-based narrowband UVB for active and limited vitiligo (The HI-Light Trial).
No full textBACKGROUND
Economic evidence for vitiligo treatments is absent.
OBJECTIVE
To determine the cost-effectiveness of (a) hand-held narrowband-UVB (NB-UVB) and (b) combination of topical corticosteroid (TCS) and NB-UVB compared to TCS for localised vitiligo.
METHODS
Cost-effectiveness analysis alongside a pragmatic, 3-arm, placebo-controlled RCT with 9 months' treatment. 517 Adults and children (aged ≥5 years) with active vitiligo affecting <10% of skin recruited from secondary care and community were randomised 1:1:1 to receive: TCS; NB-UVB; or both. Cost per successful treatment (measured on the Vitiligo Noticeability Scale) was estimated. Secondary cost-utility analyses measured QALYs using the EQ-5D-5L for those aged 11+ and CHU-9D for those aged 5 to <18.
RESULTS
Mean (SD) cost per participant was £774.4 (83.71) for NB-UVB, £813.38 (111.39) for combination treatment and £599.98 (96.18) for TCS. In analyses adjusted for age and target patch location, incremental difference in cost for combination treatment compared to TCS was £211.46 (95% CI 188.10 to 234.81), corresponding to a risk difference of 10.94% (Number-Needed-To-Treat (NNT= 9). Incremental cost was £1,932.35 per successful treatment. The incremental difference in cost for NB-UVB compared to TCS was £173.44 (95% CI 150.55 to 196.32) with a risk difference of 5.20% (NNT=19). Incremental cost was £3,335.74 per successful treatment.
CONCLUSION
Combination treatment, compared to TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost effective if decision makers are willing to pay £1,932 per additional treatment success
IM-UNITI: Three-year Efficacy, Safety, and Immunogenicity of Ustekinumab Treatment of Crohn's Disease.
No full textBACKGROUND AND AIMS
Following induction/maintenance treatment in the UNITI/IM-UNITI studies of ustekinumab for Crohn's disease, patients entered a long-term extension for up to 5 years from induction. Efficacy through 152 and safety through 156 weeks are reported.
METHODS
At IM-UNITI Week 44, 567 ustekinumab-treated patients entered the long-term extension and continued to receive blinded subcutaneous ustekinumab on their assigned dose interval, without any subsequent dose adjustment. Placebo-treated patients discontinued after study unblinding [after IM-UNITI Week 44 analyses]. Efficacy data in the long-term extension [LTE] were collected every 12 weeks [q12w] before unblinding and then at q12w/q8w dosing visits.
RESULTS
Through Week 156, 29.6% of ustekinumab-treated patients discontinued. In an intent-to-treat analysis of randomised patients from IM-UNITI Weeks 0-152, 38.0% of ustekinumab induction responders receiving the drug q12w and 43.0% q8w were in remission at Week 152. Among patients entering the long-term extension in their original randomised groups, 61.9% of q12w and 69.5% of q8w patients were in remission at Week 152. Across all ustekinumab-treated patients [randomised and non-randomised] entering the long-term extension, remission rates at Week 152 were 56.3% and 55.1% for q12w and q8w, respectively. Safety events [per 100 patient-years] were similar among all ustekinumab-treated patients entering the long-term extension and placebo [overall adverse events 389.70 vs 444.17; serious adverse events, 18.97 vs 19.54; serious infections, 4.21 vs 3.97]. Rates of antibodies to ustekinumab through Week 156 remained low, 4.6% in all randomised ustekinumab-treated patients; lowest among patients in the original randomised q8w group [2/82, 2.4%].
CONCLUSIONS
Continued treatment with subcutaneous ustekinumab maintained clinical response and remission through 3 years in a majority of patients who responded to induction therapy and was well-tolerated. ClinicalTrials.gov number NCT01369355
Impact of COVID-19 on percutaneous coronary intervention for ST-elevation myocardial infarction.
No full textBACKGROUND
The objective of the study was to identify any changes in primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in England by analysing procedural numbers, clinical characteristics and patient outcomes during the COVID-19 pandemic.
METHODS
We conducted a retrospective cohort study of patients who underwent PCI in England between January 2017 and April 2020 in the British Cardiovascular Intervention Society-National Institute of Cardiovascular Outcomes Research database. Analysis was restricted to 44 hospitals that reported contemporaneous activity on PCI. Only patients with primary PCI for STEMI were included in the analysis.
RESULTS
A total of 34 127 patients with STEMI (primary PCI 33 938, facilitated PCI 108, rescue PCI 81) were included in the study. There was a decline in the number of procedures by 43% (n=497) in April 2020 compared with the average monthly procedures between 2017 and 2019 (n=865). For all patients, the median time from symptom to hospital showed increased after the lockdown (150 (99-270) vs 135 (89-250) min, p=0.004) and a longer door-to-balloon time after the lockdown (48 (21-112) vs 37 (16-94) min, p<0.001). The in-hospital mortality rate was 4.8% before the lockdown and 3.5% after the lockdown (p=0.12). Following adjustment for baseline characteristics, no differences were observed for in-hospital death (OR 0.87, 95% CI 0.45 to 1.68, p=0.67) and major adverse cardiovascular events (OR 0.71, 95% CI 0.39 to 1.32, p=0.28).
CONCLUSIONS
Following the lockdown in England, we observed a decline in primary PCI procedures for STEMI and increases in overall symptom-to-hospital and door-to-balloon time for patients with STEMI. Restructuring health services during COVID-19 has not adversely influenced in-hospital outcomes
Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.
No full textBACKGROUND AIMS
Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. The Liver Graft Assessment Following Transplantation (L-GrAFT) risk-score estimates 3-month graft-failure-free survival (area under the receiver operator characteristic [AUROC] curve=0.83), and was superior to the binary EAD (AUROC=0.68) definition and Model for Early Allograft Function (MEAF, AUROC=0.70) in the single-center derivation cohort (DC, n=2008). We sought to externally validate L-GrAFT, and compare its prognostic performance to EAD and MEAF.
METHODS
Accuracies of L-GrAFT, EAD, and MEAF were compared in a 3-center US validation cohort (VC, n=3201), and Consortium for Organ Preservation in Europe (COPE) normothermic machine perfusion trial cohort (n=222), with comparison of characteristics to assess generalizability.
RESULTS
Compared to the DC, VC and COPE patients had lower recipient median MELD scores (18 and 14 vs 31); were less likely to require pretransplant hospitalization (23.3% and 0% vs 46.1%), renal replacement therapy (8.8% and 1.8% vs 31.7%), mechanical ventilation (3.7% and 0% vs 19.8%); and had superior 1-year overall (90% and 95% vs 84%) and graft-failure-free (88% and 93% vs 81%) survival, with a lower incidence of 3-month graft failure (7.4% and 4.0% vs. 11.1%; P<0.001 for all comparisons). Despite significant differences in cohort characteristics, L-GrAFT maintained an excellent validation AUROC of 0.78, significantly superior to the EAD (AUROC=0.68, P=0.001) and MEAF scores (AUROC=0.72, P<0.001). In post-hoc analysis of COPE NMP trial, highest tertile of L-GrAFT was significantly associated with time to liver allograft (HR 2.17, P=0.016) and Clavien ≥IIIB (HR 2.60, P=0.034) and ≥IVa (HR 4.99, P=0.011) complications, and post-LT length of hospitalization (P=0.002) and renal replacement therapy (OR 3.62, P=0.016).
CONCLUSIONS
We have validated the L-GrAFT risk score as a generalizable, highly accurate, individualized risk assessment of 3-month liver allograft failure that is superior to the existing EAD and MEAF scores. L-GrAFT may standardize grading of early hepatic allograft function, and serve as a clinical end-point in translational studies aiming to mitigate ischemia-reperfusion injury.
LAY SUMMARY
Early allograft dysfunction negatively affects outcomes following liver transplantation (LT). In independent multicenter US and European cohorts totaling 3423 patients undergoing LT, the Liver Graft Assessment Following Transplantation (L-GrAFT) risk score is validated as a superior measure of early allograft function that accurately discriminates 3-month graft failure free survival and post-LT complications