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CATALYST trial protocol: a multicentre, open-label, phase II, multiarm trial for an early and accelerated evaluation of the potential treatments for COVID-19 in hospitalised adults.
No full textINTRODUCTION
Severe SARS-CoV-2 infection is associated with a dysregulated immune response. Inflammatory monocytes and macrophages are crucial, promoting injurious, proinflammatory sequelae. Immunomodulation is, therefore, an attractive therapeutic strategy and we sought to test licensed and novel candidate drugs.
METHODS AND ANALYSIS
The CATALYST trial is a multiarm, open-label, multicentre, phase II platform trial designed to identify candidate novel treatments to improve outcomes of patients hospitalised with COVID-19 compared with usual care. Treatments with evidence of biomarker improvements will be put forward for larger-scale testing by current national phase III platform trials. Hospitalised patients >16 years with a clinical picture strongly suggestive of SARS-CoV-2 pneumonia (confirmed by chest X-ray or CT scan, with or without a positive reverse transcription PCR assay) and a C reactive protein (CRP) ≥40 mg/L are eligible. The primary outcome measure is CRP, measured serially from admission to day 14, hospital discharge or death. Secondary outcomes include the WHO Clinical Progression Improvement Scale as a principal efficacy assessment.
ETHICS AND DISSEMINATION
The protocol was approved by the East Midlands-Nottingham 2 Research Ethics Committee (20/EM/0115) and given urgent public health status; initial approval was received on 5 May 2020, current protocol version (V.6.0) approval on 12 October 2020. The MHRA also approved all protocol versions. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.
TRIAL REGISTRATION NUMBERS
EudraCT2020-001684-89, ISRCTN40580903
Adjuvant chemotherapy for perihilar cholangiocarcinoma: A population-based comparative cohort study.
No full textBACKGROUND
Data supporting routine use of adjuvant chemotherapy (AC) compared to no AC (noAC) for perihilar cholangiocarcinoma (hCCA) is unclear. This study aimed to determine whether AC improves long-term survival following resection for hCCA.
METHODS
Patients receiving resection for hCCA followed by AC or no AC from 2010 to 2016 were identified from the National Cancer Database (NCDB). Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of AC on overall survival.
RESULTS
Of 924 (56%) noAC and 719 (44%) AC, 320 noAC and 320 AC patients remained after PSM. After matching, AC was associated with improved survival (median: 28.2 vs 19.9 months, p < 0.001), which remained after multivariable adjustment (HR: 0.61, CI: 0.50-0.75, p < 0.001). On multivariable interaction analyses, the benefit of AC over no AC persisted irrespective of nodal status: N0 (HR: 0.62, CI: 0.41-0.92, p = 0.019), N1 (HR: 0.52, CI: 0.36-0.75, p = 0.001), N2 (HR: 0.31, CI: 0.11-0.90, p = 0.032), Nx (HR: 0.22, CI: 0.09-0.55, p = 0.001) and margin status: R0 (HR: 0.74, CI: 0.57-0.97, p = 0.026), R1 (HR: 0.31, CI: 0.21-0.47, p < 0.001). Stratified analysis by nodal, margin and AC status demonstrated consistent results.
CONCLUSION
AC following resection for hCCA was associated with improved survival in this study, even in margin-negative and node-negative disease. These findings suggest incorporation of AC into multimodality therapy for hCCA in all cases, where appropriate
Pelvic Ewing sarcoma: Should all patients receive pre-operative radiotherapy, or should it be delivered selectively?
No full textBACKGROUND
Locally recurrent disease following surgical resection of Ewing sarcoma (ES) confers a poor prognosis. Limited evidence is available evaluating non-selective use of pre-operative radiotherapy (RT) for patients with pelvic ES and its effect on local control and survival.
PATIENTS AND METHODS
49 consecutive patients with pelvic ES were identified retrospectively from a prospectively collated database. Patients either received non-selective pre-operative RT and surgery (n = 27), or selective post-operative RT (n = 22) (surgery alone (n = 11) or surgery and post-operative RT (n = 11)).
RESULTS
Patients who had non-selective pre-operative radiotherapy appeared to have a higher LRFS, 88.0% compared to 66.5% in the selective RT group (p = 0.096, Kaplan Meier; p = 0.028, Chi-squared). Administration of non-selective, pre-operative RT to all patients with pelvic ES elevates the LFRS to that of the good responder group (≥90% tumour necrosis and margins, p = 0.880). There was no difference in metastasis-free survival, 60.0% and 54.5% (p = 0.728) and overall survival (OS), 57.7% and 63.6% (p = 0.893). The majority of pre-operative RT patients had both good necrosis (≥90%) (p = 0.003) and widely excised tumours, 81.5% vs 59.1% (p = 0.080). Tumour volume ≥250 ml was associated with worse LRFS (p = 0.045) and post-operative complications (p = 0.017). There may be improved LRFS (p = 0.057) with pre-operative proton-beam RT compared to surgery and selective post-operative RT.
CONCLUSION
Pre-operative photon or proton-beam RT to all pelvic ES may improve LRFS compared to the selective delivery of post-operative RT. Radiotherapy delivered to all patients results in a greater percentage of highly necrotic tumours at surgical excision, enabling a greater proportion of patients with wide resection margins
Assessing the costs and outcomes of control programmes for sexually transmitted infections: a systematic review of economic evaluations.
No full textOBJECTIVE
To identify economic evaluations of interventions to control STIs and HIV targeting young people, and to assess how costs and outcomes are measured in these studies.
DESIGN
Systematic review.
DATA SOURCES
Seven databases were searched (Medline (Ovid), EMBASE (Ovid), Web of Science, PsycINFO, NHS Economic Evaluation Database, NHS Health Technology Assessment and Database of Abstracts of Reviews of Effects) from January 1999 to April 2019. Key search terms were STIs (chlamydia, gonorrhoea, syphilis) and HIV, cost benefit, cost utility, economic evaluation, public health, screening, testing and control.
REVIEW METHODS
Studies were included that measured costs and outcomes to inform an economic evaluation of any programme to control STIs and HIV targeting individuals predominantly below 30 years of age at risk of, or affected by, one or multiple STIs and/or HIV in Organisation for Economic Co-operation and Development countries. Data were extracted and tabulated and included study results and characteristics of economic evaluations. Study quality was assessed using the Philips and BMJ checklists. Results were synthesised narratively.
RESULTS
9530 records were screened and categorised. Of these, 31 were included for data extraction and critical appraisal. The majority of studies assessed the cost-effectiveness or cost-utility of screening interventions for chlamydia from a provider perspective. The main outcome measures were major outcomes averted and quality-adjusted life years. Studies evaluated direct medical costs, for example, programme costs and 11 included indirect costs, such as productivity losses. The study designs were predominantly model-based with significant heterogeneity between the models.
DISCUSSION/CONCLUSION
None of the economic evaluations encompassed aspects of equity or context, which are highly relevant to sexual health decision-makers. The review demonstrated heterogeneity in approaches to evaluate costs and outcomes for STI/HIV control programmes. The low quality of available studies along with the limited focus, that is, almost all studies relate to chlamydia, highlight the need for high-quality economic evaluations to inform the commissioning of sexual health services
Comment on "Anastomotic Techniques and Associated Morbidity in Total Minimally Invasive Transthoracic Esophagectomy: Results From the EsoBenchmark Database".
No full textIntramedullary Spinal Cord Metastasis as Initial Presentation of Malignant Melanoma: A Unique Case Report and Role of Contrast vs Non-contrast MRI in Its Diagnosis.
No full textIntramedullary spinal cord metastasis (ISCM) is a diagnostically challenging and dreadful complication of cancer. Twenty-seven cases of ISCM exclusively related to malignant melanoma have been reported so far in a recent study.On review of literature, we could not find any reported case with ISCM secondary to malignant melanoma as initial presentation. To the best of our knowledge, we are reporting the first such case. We report a case of a 71-year-old lady presenting with gradual onset of bilateral leg weakness "off legs" and lower limb paresthesias. On examination she had an upper motor neuron pattern lower limb weakness with reduced sensations to all modalities and brisk reflexes with extensor plantar responses. She was evaluated with non-contrast MRI (magnetic resonance imaging) spine which showed focal myelopathic cord signal at the conus and at the level of T10 and T11 vertebrae (radiological differential diagnosis given on MRI were B12 deficiency/inflammatory/infection). Thorough radiological scans were ordered which revealed a disseminated malignancy. A biopsy sample from gastric lesion revealed diagnosis of malignant melanoma. A repeat MRI whole spine with gadolinium contrast was done later with suspicion of spinal metastasis which has led to lower limb weakness. MRI with contrast showed an enhancing soft tissue metastatic mass lesion within conus in comparison with plain MRI done one week earlier. At present, diagnostic modalities available for diagnosing ISCM particularly secondary to melanoma do not have high specificity. Contrast MRI is the diagnostic modality of choice at present. Non-contrast MRI has low sensitivity in diagnosis of ISCM compared to contrast MRI and could potentially delay the management, especially in highly aggressive malignancies like malignant melanoma where an early diagnosis and treatment is critical for better outcome
Is a high calcific burden an indication, or a contraindication for Drug Coated Balloon?
No full textDrug coated balloons (DCB) are increasingly being used in coronary intervention. Most of their use is currently restricted to in stent restenosis, however, they are also being used to treat some de novo lesion subsets (especially small vessels) and in patients unable to take dual antiplatelet therapy beyond a month. Calcified lesions pose a significant challenge to coronary intervention from lesion preparation to the delivery of drug to the vessel wall. There are limited data on the use of DCB in calcified lesions. In this article, we have provided a detailed literature review on calcified lesions and the use of DCB including a case example
Correction to: Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort.
No full textKing cobra bite - Can early decompression prevent digital amputation?
No full textKing cobra bites are extremely rare in the western world. These bites can be fatal due to the large volume of the venom injected. We report a case of digital ischaemia from a King cobra bite in a young man who was working in a zoo in Netherlands. He was protected from systemic envenomation as he was wearing a protective glove. However, his right index finger developed subsequent gangrene and he underwent a ray amputation. The current literature on the management of snake bites to hands is reviewed and the role of early decompression discussed
Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.
No full textPURPOSE
As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway.
PATIENTS AND METHODS
This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation).
RESULTS
Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76).
CONCLUSION
Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks