Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov , NCT04384926 . Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include...
The COVID-19 pandemic has great consequences on mental health. We aimed to assess medical students’ psychological condition and influencing factors as a baseline evidence for interventions promoting their mental wellbeing. We conducted an online survey from April 8 to April 18, 2020 to examine the mental health of medical students by the nine-item Patient Health Questionnaire, seven-item Generalized Anxiety Disorder Scale, seven-item Insomnia Severity Index, and six-item Kessler psychological distress scale. Factors associated with mental health outcomes were identified by multivariable logistic regression analysis. Five hundred forty-nine students completed the survey; 341 (62.3%), 410 (74.6%), 344 (62.6%), and 379 (69%) reported anxiety, depression, insomnia, and distress, respectively. Female students, living in high COVID-19 prevalence locations, more than 25 days confinement, psychiatric consult history, and being in a preclinical level of studies had higher median scores and severe symptom levels. Multivariable logistic regression showed female gender as a risk factor for severe symptoms of anxiety (odds ratio [OR]: 1.653; 95% CI: 1.020–2.679; P = 0.042), depression (OR: 2.167; 95% CI: 1.435–3.271; P < 0.001), insomnia (OR: 1.830; 95% CI: 1.176–2.847; P = 0.007), and distress (OR: 1.994; 95% CI: 1.338–2.972; P = 0.001); preclinical level of enrollment as a risk factor for depression (OR: 0.679; 95% CI: 0.521–0.885; P = 0.004), insomnia (OR: 0.720; 95% CI: 0.545–0.949; P = 0.02), and distress (OR: 0.650; 95% CI: 0.499–0.847; P = 0.001), whereas living in high COVID-19 prevalence locations was a risk factor for severe anxiety (OR: 1.628; 95% CI: 1.090–2.432; P = 0.017) and depression (OR: 1.438; 95% CI: 1.002–2.097; P = 0.05). Currently, medical students experience high levels of mental health symptoms, especially female students, those at a preclinical level and living in regions with a high prevalence of COVID-19 cases. Screening for mental health issues, psychological support, and long-term follow-up could alleviate the burden and protect future physicians.
The molybdopterin cofactor (MoCF) is required for the activity of a variety of oxidoreductases. The xanthine oxidase class of molybdoenzymes requires the MoCF to have a terminal, cyanolysable sulphur ligand. In the sulphite oxidase/nitrate reductase class, an oxygen is present in the same position. Mutations in both the ma‐l gene of Drosophila melanogaster and the hxB gene of Aspergillus nidulans result in loss of activities of all molybdoenzymes that necessitate a cyanolysable sulphur in the active centre. The ma‐l and hxB genes encode highly similar proteins containing domains common to pyridoxal phosphate‐dependent cysteine transulphurases, including the cofactor binding site and a conserved cysteine, which is the putative sulphur donor. Key similarities were found with NifS, the enzyme involved in the generation of the iron–sulphur centres in nitrogenase. These similarities suggest an analogous mechanism for the generation of the terminal molybdenum‐bound sulphur ligand. We have identified putative homologues of these genes in a variety of organisms, including humans. The human homologue is located in chromosome 18.q12.
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